-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs are involved in human carcinogenesis and cancer progression. Our previous study has shown that loss of miR-338-3p expression is associated with clinical aggressiveness of hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of miR-338-3p remain unknown in HCC. To determine whether and how miR-338-3p influences liver cancer cell invasion, we studied miR-338-3p in the liver cancer cell lines, and we found that miR-338-3p is down-regulated in treated cells. Forced expression of miR-338-3p in SK-HEP-1 cells suppressed cell migration and invasion, whereas inhibition of miR-338-3p in SMMC-7721 cells induced cell migration and invasion. Furthermore, smoothened (SMO) was identified as a direct target of miR-338-3p. Forced expression of miR-338-3p down-regulated SMO and matrix metalloproteinase (MMP)-9 expression, but inhibition of miR-338-3p up-regulated SMO and MMP9 expression. However, small interfering RNA targeted SMO reversed the effects induced by blockade of miR-338-3p. SMO and MMP9 were overexpressed and associated with invasion and metastasis in HCC tissues. These data indicate that miR-338-3p suppresses cell invasion by targeting the smoothened gene in liver cancer in vitro and miR-338-3p might be a novel potential strategy for liver cancer treatment.
The Journal of Pathology 02/2011; 225(3):463-72. · 6.32 Impact Factor
-
Kar Lok Kong,
Dora L Kwong,
Li Fu,
Tim Hon Man Chan,
Leilei Chen,
Haibo Liu,
Yan Li,
Ying-Hui Zhu, Jiong Bi,
Yan-Ru Qin,
Simon Ying Kit Law,
Xin-Yuan Guan
[show abstract]
[hide abstract]
ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G(1)-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of MMP7. These findings were consistent with evidence derived from clinical samples, where UPK1A downregulation was correlated with lymph node metastasis (P = 0.009), stage (P = 0.015), and overall survival (P < 0.0001). Indeed, multivariate cyclooxygenase regression analysis showed that UPK1A was an independent prognostic factor for overall survival. Taken together, our findings define a function for UPK1A as an important TSG in ESCC development.
Cancer Research 10/2010; 70(21):8832-41. · 7.86 Impact Factor
-
Xinhui Fu,
Qian Wang,
Jingsong Chen,
Xiaohui Huang,
Xilin Chen,
Liangqi Cao,
Haoxiang Tan,
Wen Li,
Longjuan Zhang, Jiong Bi,
Qiao Su,
Lianzhou Chen
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present study is to explore possible role of miR-221 in the pathogenesis of HCC. Matched HCC and adjacent non-cancerous samples were assayed for the expression of miR-221 and three G1/S transition inhibitors: p27(Kip1), p21(WAF1/Cip1)and TGF-β1 by in situ hybridization and immunohistochemistry respectively. p27(Kip1) is one of miR-221's proven targets. Real time qRT-PCR was used to investigate miR-221 and p27(Kip1) transcripts in different clinical stages. Western blotting was used to analyze the expression levels of p27(Kip1) protein in different clinical stages. In result, miR-221 and TGF-β1 are frequently up-regulated in HCC, while p27(Kip1) and p21(WAF1/Cip1) proteins are frequently down-regulated. Moreover, miR-221 and p27(Kip1)'s expression correlated with metastasis and miR-221's expression also correlated with tumor size. Both of p21(WAF1/Cip1)and TGF-β1's expression correlated with tumor differentiations. miR-221's upregulation and p27(Kip1)'s downregulation were significantly associated with tumor stages and metastasis. In conclusion, miR-221 is important in tumorigenesis of HCC, possibly by specifically down-regulating p27(Kip1), a cell-cycle inhibitor. These results indicate miR-221 as a new therapeutic target in HCC.
Molecular Biology Reports 02/2010; 38(5):3029-35. · 2.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Studies have shown that focal adhesion kinase (FAK) is overexpressed in several human tumors and plays an important role in tumor progression. However, the role and underlying mechanisms of FAK in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we examined FAK and phosphorylated FAK Tyr397 expression in a large series of HCCs. We found that both FAK and phosphorylated FAK Tyr397 were overexpressed in HCC samples and HCC cell lines. Increased FAK and phosphorylated FAK Tyr397 expressions were correlated with tumor stage, vascular invasion and intrahepatic metastasis in HCC. Furthermore, HCC cell adhesion, migration and invasion were substantially impaired by siRNA-mediated knockdown of FAK expression, whereas cell growth, apoptosis and cell cycle distribution were not affected. In addition, depletion of FAK induced a significant reduction in expressions and activities of both MMP-2 and MMP-9. Taken together, FAK contributes to invasion and metastasis of HCC partly through regulating expressions and activations of both MMP-2 and MMP-9, suggesting FAK could be a promising therapeutic target for HCC.
Clinical and Experimental Metastasis 02/2010; 27(2):71-82. · 3.52 Impact Factor
-
Jiong Bi,
Sze-Hang Lau,
Zi-Li Lv,
Dan Xie,
Wen Li,
Ying-Rong Lai,
Jue-Min Zhong,
Hui-qun Wu,
Qiao Su,
Yu-long He,
Wen-Hua Zhan,
Jian-Ming Wen,
Xin-Yuan Guan
[show abstract]
[hide abstract]
ABSTRACT: YKL-40 is a growth factor for connective tissue cells and a migration factor for endothelial cells. Elevated serum level of YKL-40 has been associated with poor prognosis in many cancers. However, the status of YKL-40 expression and its clinical/prognostic significance in gastric cancer are unclear. In this study, the expression of YKL-40 was studied by immunohistochemistry in gastric cancer tissue microarray containing 172 primary gastric cancer cases and 70 adjacent nonneoplastic mucosa specimens. The correlations between YKL-40 expression and clinicopathologic features, as well as activation of PI3K/Akt pathways were addressed. Expression of YKL-40 was significantly higher in gastric cancer tissues than that in adjacent nonneoplastic tissues. Overexpression YKL-40 was found in 28.4% of gastric cancers and was significantly associated with tumor invasion (P = .007) and lymph node metastasis (P = .009). For survival study, overexpression of YKL-40 was significantly associated with worse outcome (P = .001). When known clinical variables were added to a multivariate analysis, TNM stage, tumor size, and overexpression of YKL-40 emerged as independent prognostic factors. Further study indicated that the oncogenic function of YKL-40 might be through the activation of Akt pathway. These results suggest that overexpression of YKL-40 is correlated with the aggressive behavior of tumor cells, which could be used as an independent molecular marker for the predicting poor prognosis of patients with gastric cancer.
Human pathology 09/2009; 40(12):1790-7. · 3.03 Impact Factor
-
Betty H. Y. Chow,
Daniel T. T. Chua,
Jonathan S. T. Sham,
Min-Yue Zhang,
Louis W. C. Chow, Jiong Bi,
Ning-Fang Ma,
Dan Xie,
Wings T. Y. Loo,
Jackie M. W. Fung,
Li Fu,
Xin-Yuan Guan
[show abstract]
[hide abstract]
ABSTRACT: Adjuvant chemotherapy alongside radiotherapy is one of the effective therapies in nasopharyngeal carcinoma (NPC) treatment. However, the appearance of drug resistance is a major obstacle for anti-cancer chemotherapy and often causes failure of the chemotherapy. In this study, a drug-resistant gene annexin I (ANX-I) was identified by comparing differentially expressed proteins between a cisplatin (CDDP)-resistant NPC cell line CNE2-CDDP and parental CNE2 cells using 2-DE. When ANX-I was transfected into CNE2 cells, the CDDP resistance of CNE2 cells was dramatically increased. The drug-resistant ability of ANX-I was demonstrated by both in vitro and in vivo assays. The association of ANX-I expression with clinical features was also investigated. Increased expression of ANX-I was significantly associated with disease relapse in NPC (p<0.05). In breast and gastric cancer, increased expression of ANX-I was significantly associated with drug resistance (p<0.001) and poor prognosis (p<0.001), respectively. Taken together, our findings suggest that ANX-I plays an important role in drug resistance.
PROTEOMICS - CLINICAL APPLICATIONS 06/2009; 3(6):654 - 662. · 1.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: High epidermal growth factor receptor (EGFR) expression in the primary tumor predicts poor survival in colorectal cancer. However, EGFR expression may be discordant in primary tumor versus nodal or distant metastasis. We evaluated prognostic values of high EGFR expression in nodal metastasis versus primary tumor tissue.
Tissue microarrays from 94 surgically resected colorectal primary tumors were analyzed for EGFR expression using immunohistochemistry along with 49 paired positive metastatic nodes and 19 distant metastases. Proportional odds regression and log-rank tests described the association of tumor stage and survival with EGFR, dichotomized to low expression (0, 1) versus high expression (2, 3).
High EGFR expression rates in the primary tumor, metastatic lymph node and distant metastases were 18%, 24%, and 21%, respectively. The concordance rate was 71% for stage III/IV patients. High EGFR expression in primary tumor was associated with higher tumor stage (odds ratio 4.3, P = 0.005) and thus predicted poor survival (P = 0.046). High EGFR expression in the primary tumor was not associated with survival in patients with stage III or IV disease, whereas high EGFR expression in metastatic lymph nodes was associated with relatively poor survival (P = 0.005), for both stage III (P = 0.002) and stage IV patients (P = 0.014). Concordant high EGFR expression in primary tumor and lymph nodes conferred added risk of death (P = 0.003), conversely, concordant EGFR-negative primary tumor and lymph node was protective (P = 0.097).
EGFR expression may be discordant among primary, nodes, and metastases in colorectal cancer. High EGFR expressions in metastatic lymph nodes seem to be more accurate in predicting survival than in primary or metastatic tissues.
American journal of clinical oncology 06/2009; 32(3):245-52. · 2.21 Impact Factor
-
Xiao-Hui Huang,
Qian Wang,
Jing-Song Chen,
Xin-Hui Fu,
Xi-Lin Chen,
Lian-Zhou Chen,
Wen Li, Jiong Bi,
Long-Juan Zhang,
Qian Fu,
Wen-Tao Zeng,
Liang-Qi Cao,
Hao-Xiang Tan,
Qiao Su
[show abstract]
[hide abstract]
ABSTRACT: Aim: Recent studies have underlined causative links between microRNA (miRNA) deregulation and cancer development. However, the relevance of abnormally expressed miRNA to tumor biology has not been well understood in hepatocellular carcinoma (HCC). Methods: A bead-based miRNA expression profiling method was performed on 20 pairs of surgically removed HCC and adjacent non-tumorous tissue (NT). Special miR-338 downregulations and miR-338 associated with clinical characteristics was validated in an extended samples set of 36 paired HCC and adjacent non-tumorous liver tissues by real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: Out of our bead-based microarray data, 12 upregulated and 19 downregulated miRNA were found to be associated with HCC. Further characterization of miRNA-338, in which 20 pairs of the samples were clustered clearly into two groups according to expression of miR-338, revealed that the level of miR-338 expression can be associated with clinical aggressiveness, such as, tumor size, tumor-node-metastasis stage, vascular invasion and intrahepatic metastasis. These results were validated by real-time RT-PCR analysis. Conclusion: Our study suggests that miRNA expression could have relevance to the clinical behavior of HCC and that the bead-based miRNA expression profiling method might be a suitable system to assay miRNA expression in large-scale diagnostic trails.
Hepatology Research 04/2009; 39(8):786-94. · 2.20 Impact Factor
-
Jiong Bi,
Sze-Hang Lau,
Liang Hu,
Hui-Lan Rao,
Hai-Bo Liu,
Wen-Hua Zhan,
Gong Chen,
Jian-Ming Wen,
Qian Wang,
Bin Li,
Xin-Yuan Guan
[show abstract]
[hide abstract]
ABSTRACT: Deletion of 19p13 is one of the most frequent genetic changes in gastric carcinoma (GC), implying the existence of a tumor suppressor gene (TSG) that plays an important role in GC development. To identify the candidate TSG at 19p, array-comparative genomic hybridization (CGH) was applied to study DNA copy-number changes on chromosomes 3, 5p, 13, 16q and 19. The result showed that gains of 16q21, 19q13.1, 5p15.1 and 3q26.31, and losses of 3p21.32, 3p22.2, 19q13.33 and 19p13.3, were frequently detected by array-CGH. One candidate TSG, ZIP kinase (ZIPK), at 19p13.3 was further characterized by immunohistochemistry using a tissue microarray containing 172 primary GCs. Downregulation of ZIPK was detected in 111/162 informative GCs, which was significantly associated with invasion, metastasis and poorer prognosis of GC. To investigate the association of the downregulation of ZIPK with apoptosis, apoptosis assay (TUNEL) was used to compare the apoptotic index between GCs with normal expression and downregulation of ZIPK. TUNEL assay showed that the apoptotic index in GCs with normal ZIPK expression was significantly higher than that in GCs with downregulation of ZIPK (p < 0.001), indicating that ZIPK plays an important pro-apoptotic role in GC. Taken together, we demonstrated here that ZIPK is a tumor suppresser gene and plays an important role in GC development through its pro-apoptotic function. Downregulation of ZIPK can be used to evaluate tumor invasiveness, metastasis and to predict survival of GC.
International Journal of Cancer 11/2008; 124(7):1587-93. · 5.44 Impact Factor
-
Jing-song Chen,
Qian Wang,
Xin-hui Fu,
Xiao-Hui Huang,
Xi-lin Chen,
Liang-qi Cao,
Lian-zhou Chen,
Hao-xiang Tan,
Wen Li, Jiong Bi,
Long-juan Zhang
[show abstract]
[hide abstract]
ABSTRACT: Aim: To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC).Methods: PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC.Results: In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index (P < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively (P < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2.Conclusions: PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.
Hepatology Research 10/2008; 39(2):177 - 186. · 2.20 Impact Factor
-
Xinhui Fu,
Qian Wang,
Xilin Chen,
Xiaohui Huang,
Liangqi Cao,
Haoxiang Tan,
Wen Li,
Longjuan Zhang, Jiong Bi,
Qiao Su,
Lianzhou Chen
[show abstract]
[hide abstract]
ABSTRACT: Aberrant activation of Hedgehog signaling pathway leads to pathological consequences in a variety of human tumors. PTCH (PTCH1), the receptor of Hedgehog pathway, is reported to function as a gatekeeper in tumor formation. Here we report, by semi-quantitative RT-PCR, PTCH expression was found in 38 hepatocellular carcinoma (HCC) patients (66%). Evidences from real time quantitative RT-PCR further indicate that compared to their matched nontumorous liver tissue, PTCH exhibit a higher expression in well and moderate differentiated tumor, but a lower expression in poorly differentiated tumor. Immunohistochemical staining showed PTCH protein was detected in the cytoplasm of 56.3% HCC samples (9/16). For the first time, we investigate the polymorphisms of PTCH in HCC. First we sequenced the recognized mutation hot spots regions of PTCH of 38 HCC samples. Two previously reported single nucleotide polymorphisms (SNPs) and a novel SNP A1056G were identified. Then we examined these three SNPs in 171 HCC samples and 162 normal liver samples. However, statistic analysis showed none of these SNPs was statistically significant for association with HCC. In conclusion, our data suggest that PTCH is involved in early stage tumor development and the Hh pathway in Chinese HCC is activated by ligand expression but not by mutation.
Experimental and Molecular Pathology 07/2008; 84(3):195-9. · 2.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer, especially estrogen receptor (ER)-negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER-negative breast cancers express high levels of interleukin-8 (IL-8), whereas their ER-positive counterparts do not. IL-8 is a multi-functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL-8 in ER-negative breast cancer progression by using RNA interference to specifically knockdown IL-8 expression in ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468. In vitro, suppression of IL-8 led to significant reductions in cell invasion (p<0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL-8 significantly reduced the microvessel density (p<0.05), and markedly reduced neutrophil infiltration into the tumors (p<0.05). In contrast to in vitro observations, suppression of IL-8 promoted tumor growth in nude mice (p<0.05). Our results imply that the complex roles of IL-8 in the regulation of ER-negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL-8.
International Journal of Cancer 12/2007; 121(9):1949-57. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interleukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.
Interfering pRNA-IL-8 and the control was transfected into ER (-) MDA-MB-231. The proliferation, cell apotosis, and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).
In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P < 0.001), but had no effect on cell proliferation (P > 0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P = 0.001, P < 0.001). Less metastasis was found in transfected cells compared with negatively transfected cells (0% vs 80%, P = 0.048). Nevertheless, we observed less MVD in transfected cells compared with control in nude mice (P < 0.001).
IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may be correlated with neutrophils infiltration induced by IL-8.
Chinese medical journal 10/2007; 120(20):1766-72. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effects of ulinastatin (UTI), a urinary trypsin inhibitor, on the promotion of the function recovery of transplanted kidney, especially for those with acute tubular necrosis (ATN).
Thirty patients underwent general cadaver kidney transplantation were randomly allocated to 2 equal groups: Group A (UTI-treatment group) and Group B (control group). 40 patients whose allografts were presumed to be with acute tubular necrosis (ATN) were also divided into 2 equal groups: Group C (UTI-treatment group) and Group D (control group). Group A and C were given ulinastatin perioperatively. 1, 3, 7, and 10 days after the transplantation blood and urine samples were collected. The levels of urine and blood alpha1-microglobulin (MG) were detected by radioimmunoassay. Blood IL-8, IL-10, and serum creatine (sCr) were detected by ELISA.
Within 10 days after the transplantation the urine volume of Group A significantly increased, especially the urine volumes of days 2, 6, 7, 9, and 10 were significant greater than those of Group B (all P < 0.05). The levels of blood IL-8 of Group A in days 1 and 3 were (93.75 +/- 31.5) ng/L and (41.98 +/- 24.01) ng/L respectively, significantly lower than those of Group B [(135.0 +/- 31.2) ng/L and (78.34 +/- 76.39) ng/L respectively, both P < 0.05]. The levels of urine alpha1-MG in days 1 and 3 were (69.89 +/- 32.60) mg/L and (35.33 +/- 34.54) mg/L respectively, both significantly lower than those of Group B [(91.15 +/- 28.39) mg/L and (65.84 +/- 33.38) mg/L respectively, both P < 0.05]. In group C, the levels of blood alpha1-MG in days 7 and 10 of Group C were (118.26 +/- 41.23) mg/L and (99.49 +/- 68.63) mg/L respectively, both significantly lower than those of Group D [(187.15 +/- 55.23) mg/L and (151.27 +/- 87.42) mg/L respectively, both P < 0.05]. The urine alpha1-MG in days 7 and 10 were (39.89 +/- 22.32) mg/L and (38.21 +/- 20.36) mg/L respectively, both significantly lower than those of Group D [(67.34 +/- 21.56) mg/L and (62.26 +/- 29.24) mg/L respectively, both P < 0.05]. Compared to Group D, the increasing tendency of blood IL-8 was better suppressed in Group C, and the diuretic phases appeared earlier.
UTI significantly improves the microcirculation, protects the tubule of transplanted kidney, increases the volume of urine, inhibits the inflammatory response, and promotes the recovery of ATN during the perioperative period of kidney transplantation.
Zhonghua yi xue za zhi 08/2007; 87(32):2241-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer, especially estrogen receptor (ER)-negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER-negative breast cancers express high levels of interleukin-8 (IL-8), whereas their ER-positive counterparts do not. IL-8 is a multi-functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL-8 in ER-negative breast cancer progression by using RNA interference to specifically knockdown IL-8 expression in ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468. In vitro, suppression of IL-8 led to significant reductions in cell invasion (p < 0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL-8 significantly reduced the microvessel density (p < 0.05), and markedly reduced neutrophil infiltration into the tumors (p < 0.05). In contrast to in vitro observations, suppression of IL-8 promoted tumor growth in nude mice (p < 0.05). Our results imply that the complex roles of IL-8 in the regulation of ER-negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL-8. © 2007 Wiley-Liss, Inc.
International Journal of Cancer 07/2007; 121(9):1949 - 1957. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effects of rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on the expression of the phosphatase and tensin homologue deleted on chromosome 10 gene (PTEN) and cell growth in hepatocellular carcinoma cells, as well as the underlying mechanisms of these effects.
RT-PCR and Western blotting analyses were performed to detect transcription and the expression of PTEN in Hep3B cells treated with rosiglitazone. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to evaluate cell growth. Flow cytometry, DNA fragmentation analysis, caspase enzymatic assay, and Hoechst 33258 staining were used to determine cell apoptosis. Furthermore, small interfering RNA was used to suppress PTEN expression.
Rosiglitazone increased the expression of PTEN in a dose- and time-dependent manner through the PPARgamma-dependent signal transduction pathway. PTEN upregulation was concomitant with a decreased level of Akt phosphorylation, subsequently resulting in cell growth inhibition and apoptosis in Hep3B cells. PTEN knockdown dramatically blocked these effects of rosiglitazone. Moreover, the exposure of cells to rosiglitazone activated caspases-9 and -3 during apoptotic proceeding.
Thus, upregulation of PTEN is involved in the inhibition of cell growth and the induction of cell apoptosis by rosiglitazone, suggesting that rosiglitazone may be useful in liver cancer therapy via apoptosis.
Acta Pharmacologica Sinica 07/2007; 28(6):879-87. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been suggested that the steroid receptor coactivatior-3 (SRC-3) gene, also known as AIB1, ACTR, RAC3, p/CIP and TRAM-1, located at 20q12, plays an oncogenic role in several types of human cancers. In this study, we examined the encoded protein expression of SRC-3 and its copy number in 221 human esophageal squamous cell carcinomas (ESCCs). In this ESCC series, the overexpression and increased copy number of SRC-3 gene was detected in 46 and 13% of ESCCs, respectively. In addition, overexpression of SRC-3 was observed more frequently in primary ESCCs in late T stages (T3/T4) than that in earlier T1/T2 stages (P<0.05), but no significant association of expression of SRC-3 and status of lymph node metastases was observed (P>0.05). These results suggest that overexpression of SRC-3, caused by gene amplification/gain or other molecular mechanisms, might provide a selective advantage for the development and local invasion of certain subsets of ESCC. In addition, a significant correlation (P<0.05) of overexpression of SRC-3 with increased cell proliferation (through detection of Ki-67 expression) was observed in these ESCCs. These findings suggest a potential role of SRC-3 in the control of ESCC cell proliferation; such may be responsible, at least in part, for tumorigenesis and/or progression of ESCC.
Cancer Letters 01/2007; 245(1-2):69-74. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We used methylation-sensitive restriction fingerprinting (MSRF) to identify novel CpG (5'-CG-3' palindrome; p, phosphate group)-rich sequences that are methylated differentially between the hepatocellular carcinoma (HCC) genomes and adjacent nontumorous liver tissues. A 199-base-pair sequence methylated in HCC tumor tissue was isolated and showed high homology to the 5' CpG island of the zinc fingers and homeoboxes protein 2 (ZHX2) gene. By using bisulfite sequencing, we confirmed that hypermethylation of the 5' CpG island of ZHX2 occurred in some HCC and HepG2 cell lines but not in 6 normal liver tissue samples. By using methylation-specific polymerase chain reaction, we detected methylation of the 5' CpG island of ZHX2 in 46.9% of the HCCs. Reverse transcription-polymerase chain reaction demonstrated that ZHX2 messenger RNA (mRNA) was expressed in all 6 normal liver tissue samples but in only 13.3% of the methylated HCCs. Treatment of HepG2 with 5-aza-deoxycytidine could demethylate the promoter and increase ZHX2 mRNA expression. These results suggest that hypermethylation-mediated silencing of ZHX2 is an epigenetic event involved in HCC.
American Journal of Clinical Pathology 06/2006; 125(5):740-6. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.
Human Pathlogy 07/2005; 36(7):777-83. · 2.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.
Human Pathology.
