-
Yun-Feng Qi,
Yan-Xin Huang,
Hong-Yan Wang,
Yu Zhang,
Yong-Li Bao,
Lu-Guo Sun, Yin Wu,
Chun-Lei Yu,
Zhen-Bo Song,
Li-Hua Zheng,
Ying Sun,
Guan-Nan Wang,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are multifunctional cytokines that regulate immune responses, cell proliferation, and tumour development and progression, which frequently have functionally opposing roles. The cellular responses to both cytokines are activated via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. During the past 10 years, the crosstalk mechanism between the IFN-gamma and IL-6 pathways has been studied widely and several biological hypotheses have been proposed, but the kinetics and detailed crosstalk mechanism remain unclear. RESULTS: Using established mathematical models and new experimental observations of the crosstalk between the IFN-gamma and IL-6 pathways, we constructed a new crosstalk model that considers three possible crosstalk levels: (1) the competition between STAT1 and STAT3 for common receptor docking sites; (2) the mutual negative regulation between SOCS1 and SOCS3; and (3) the negative regulatory effects of the formation of STAT1/3 heterodimers. A number of simulations were tested to explore the consequences of cross-regulation between the two pathways. The simulation results agreed well with the experimental data, thereby demonstrating the effectiveness and correctness of the model. CONCLUSION: In this study, we developed a crosstalk model of the IFN-gamma and IL-6 pathways to theoretically investigate their cross-regulation mechanism. The simulation experiments showed the importance of the three crosstalk levels between the two pathways. In particular, the unbalanced competition between STAT1 and STAT3 for IFNR and gp130 led to preferential activation of IFN-gamma and IL-6, while at the same time the formation of STAT1/3 heterodimers enhanced preferential signal transduction by sequestering a fraction of the activated STATs. The model provided a good explanation of the experimental observations and provided insights that may inform further research to facilitate a better understanding of the cross-regulation mechanism between the two pathways.
BMC Bioinformatics 02/2013; 14(1):41. · 2.75 Impact Factor
-
Yun-Chao Wang,
Yu-Wei Zhang,
Li-Hua Zheng,
Yong-Li Bao, Yin Wu,
Chun-Lei Yu,
Lu-Guo Sun,
Yu Zhang,
Yan-Xin Huang,
Ying Sun,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: A new 2,5-diketopiperazine, (R)-2-(2-(furan-2-yl)-oxoethyl)-octahydropyrrolo[1,2-a]pyrazine-1,4-dione, and seven known compounds were isolated from the ethyl acetate extract of liquid fermentation broth of Armillaria mellea. The structures of the isolated compounds were established from NMR and HR-MS data. The absolute configuration of the new compound was established by comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD data.
Journal of Asian natural products research 01/2013; · 0.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A reversed phase high performance liquid chromatography method coupled with a diode array detector (HPLC-DAD) was developed for the first time for the simultaneous determination of 9 flavonoids in Senecio cannabifolius, a traditional Chinese medicinal herb. Agilent Zorbax SB-C18 column was used at room temperature and the mobile phase was a mixture of acetonitrile and 0.5% formic acid (v/v) in water in the gradient elution mode at a flow-rate of 1.0mlmin(-1), detected at 360nm. Validation of this method was performed to verify the linearity, precision, limits of detection and quantification, intra- and inter-day variabilities, reproducibility and recovery. The calibration curves showed good linearities (R(2)>0.9995) within the test ranges. The relative standard deviation (RSD) of the method was less than 3.0% for intra- and inter-day assays. The samples were stable for at least 96h, and the average recoveries were between 90.6% and 102.5%. High sensitivity was demonstrated with detection limits of 0.028-0.085μg/ml for flavonoids. The newly established HPLC method represents a powerful technique for the quality assurance of S. cannabifolius.
Journal of pharmaceutical and biomedical analysis 12/2012; 76C:44-48. · 2.45 Impact Factor
-
Ling-Ying Lin,
Yong-Li Bao,
Yong Chen,
Lu-Guo Sun,
Xiao-Guang Yang,
Biao Liu,
Zhong-Xiang Lin,
Yu-Wei Zhang,
Chun-Lei Yu, Yin Wu,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: The high biological activity of dehydroabietylamine derivatives has been reported previously. In this study, we aimed to screen 73 dehydroabietylamine derivatives as potential candidate inhibitors in liver cancer cells. Initially, the compounds structural activity relationship analysis was explored and N-benzoyl-12-nitrodehydroabietylamine-7-one (compound 81) was shown to have significant growth inhibitory activity in the human liver carcinoma cell line, HepG2. Further research into the anti-proliferative effect on HepG2 cells mediated by compound 81 was undertaken. The results suggest that compound 81 effectively induced apoptosis in HepG2 cells characterized by nuclear staining of DAPI, TUNEL assay and the activation of caspase-3. A decreased level of anti-apoptotic protein Bcl-2 and increased apoptotic Bax were also observed. Furthermore, Ki-67 protein staining and the BrdU incorporation assay showed that compound 81 significantly inhibited the proliferation of HepG2 cells. Cell cycle components analysis found that expression of cyclin D1 and cyclin B1 was reduced in HepG2 cells with compound 81 treatment, whereas the content of p21(Waf1/Cip1) was increased. Taken together, our data indicate that compound 81 induces apoptosis and inhibits proliferation in HepG2 cells, and may be a promising candidate in the development of a novel class of antitumor agents.
Chemico-biological interactions 06/2012; 199(2):63-73. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The title compound {systematic name: 4-[(3S,5S,8R,9S,10R,13R,14S,17S)-3,5,14-trihy-droxy-10,13-dimethyl-hexa-deca-hydro-1H-cyclo-penta-[a]phenanthren-17-yl]furan-2(5H)-one}, C(23)H(34)O(5), was isolated from the roots of Periploca sepium Bunge, a famous Chinese traditional herbal medicine. The three six-membered rings adopt chair conformations, the cyclo-pentane ring displays an approximate envelope conformation (with the C atom bearing the methyl substituent at the flap) and the five-membered lactone ring adopts an essentially planar [maximum deviation of 0.004 (8) Å] conformation. In the crystal, mol-ecules are linked into helical chains along [010] by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions. Two intra-molecular O-H⋯O hydrogen bonds are also present.
Acta Crystallographica Section E Structure Reports Online 06/2012; 68(Pt 6):o1582-3. · 0.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A novel, simple and specific normal-phase liquid chromatography (NPLC) method has been developed for simultaneous determination
of the four lathyrane diterpenoids, lathyrol-5,15-diacetate-3-benzoate (1, L3), lathyrol-5,15-diacetate-3,7-dibenzoate (2, L2), Δ6,17-epoxide-5,15-diacetate-3-phenylacetate (3, L1), lathyrol-5,15-diacetate-3-nicotinate (4, L8) in the hexane extract of the seeds of Euphorbia lathyris and “ZI-JIN-DING” pastille. The method showed good linearity for the four analytes (r
2>0.99), the intra-day and inter-day variations (RSD) were less than 3%, and the recoveries ranged from 99.4 to 100.6%. This
method was successfully used to determine the four lathyrane diterpenoids in the seeds of Euphorbia lathyris and “ZI-JIN-DING” pastille, and could be applied for their quality control.
KeywordsColumn liquid chromatography-NPLC-DAD-Lathyrane diterpenoids-
Euphorbia lathyris L. and “ZI-JIN-DING” pastille
Chromatographia 04/2012; 71(7):617-622. · 1.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiostatin is a 38 ku circulating angiogenesis inhibitor purified from the serum and urine of mice bearing a murine Lewis
lung carcinoma. It is regarded as an internal fragment of plasminogen containing the first 4 Kringle structures.In vitro, angiostatin specifically inhibits endothelial cell proliferation.In vivo, it inhibits angiogenesis and suppresses the growth of such primary tumors as Lewis lung carcinoma and hemangioendotheliolma
in mice.
Keywordsangiostatin-angiogenesis-endothelial cell-anti-tumor
Chinese Science Bulletin 04/2012; 46(6):454-459. · 1.32 Impact Factor
-
Yao Yao,
Yu-Wei Zhang,
Lu-Guo Sun,
Biao Liu,
Yong-Li Bao,
Hua Lin,
Yu Zhang,
Li-Hua Zheng,
Ying Sun,
Chun-Lei Yu, Yin Wu,
Guan-Nan Wang,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: Juglanthraquinone C (1,5-dihydroxy-9,10-anthraquinone-3-carboxylic acid, JC), a naturally occurring anthraquinone isolated from the stem bark of Juglans mandshurica, shows strong cytotoxicity in various human cancer cells in vitro. Here, we first performed a structure-activity relationship study of six anthraquinone compounds (JC, rhein, emodin, aloe-emodin, physcion and chrysophanol) to exploit the relationship between their structural features and activity. The results showed that JC exhibited the strongest cytotoxicity of all compounds evaluated. Next, we used JC to treat several human cancer cell lines and found that JC showed an inhibitory effect on cell viability in dose-dependent (2.5-10 μg/ml JC) and time-dependent (24-48 h) manners. Importantly, the inhibitory effect of JC on HepG2 (human hepatocellular carcinoma) cells was more significant as shown by an IC(50) value of 9 ± 1.4 μg/ml, and 36 ± 1.2 μg/ml in L02 (human normal liver) cells. Further study suggested that JC-induced inhibition HepG2 cell proliferation was associated with S phase arrest, decreased protein expression of proliferation marker Ki67, cyclin A and cyclin-dependent kinase (CDK) 2, and increased expression of cyclin E and CDK inhibitory protein Cip1/p21. In addition, JC significantly triggered apoptosis in HepG2 cells, which was characterized by increased chromatin condensation and DNA fragmentation, activation of caspase-9 and -3, and induction of a higher Bax/Bcl2 ratio. Collectively, our study demonstrated that JC can efficiently inhibit proliferation and induce apoptosis in HepG2 cells.
Apoptosis 04/2012; 17(8):832-41. · 4.07 Impact Factor
-
Cong Fan,
Yan-Xin Huang,
Yong-Li Bao,
Lu-Guo Sun, Yin Wu,
Chun-Lei Yu,
Yu Zhang,
Zhen-Bo Song,
Li-Hua Zheng,
Ying Sun,
Guan-Nan Wang,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR.
International Journal of Molecular Sciences 01/2012; 13(12):17185-209. · 2.60 Impact Factor
-
Yu-Yin Li,
Yong-Li Bao,
Zhen-Bo Song,
Lu-Guo Sun,
Ping Wu,
Yu Zhang,
Cong Fan,
Yan-Xin Huang, Yin Wu,
Chun-Lei Yu,
Ying Sun,
Li-Hua Zheng,
Guan-Nan Wang,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: Testes-specific protease 50 (TSP50), a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO) cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood.
To delineate whether the threonine protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-κBIκBα complex, which is necessary for TSP50 to perform its function in cell proliferation.
Our data highlight the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation.
PLoS ONE 01/2012; 7(5):e35030. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Folate-functionalized polyoxometalate nanoparticles have unique oxidase-like activity, which can facilitate the fast oxidation of organic dyes without using any oxidizing agents or peroxidases especially at neutral pH conditions. This nanoparticle could be used as an agent in colorimetric multiplexed immunoassays.
Chemical Communications 03/2011; 47(10):2940-2. · 6.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of MDR1 promoter, and the transfected cells were used as models to screen for candidate multidrug resistance inhibitors from over 300 purified naturally occurring compounds extracted from plants and animals. Dioscin was found to have an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line (HepG2/adriamycin) was used to validate the activity of multidrug resistance reversal by Dioscin. Results showed that Dioscin could decrease the resistance degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein expression, as well as increase the accumulation of adriamycin in HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results suggest that Dioscin is a potent multidrug resistance reversal agent and may be a potential adjunctive agent for tumor chemotherapy.
European journal of pharmacology 03/2011; 654(2):129-34. · 2.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been suggested that deregulation of activin signaling contributes to tumor formation. Activin signaling is blocked in cancer cells due to the complex formed by Cripto-1, activin, and activin receptor type II (ActRII). In this study, the authors used a mammalian two-hybrid system to construct a drug screening model to obtain a small molecular inhibitor capable of interrupting the interaction between Cripto-1 and ActRII. They screened 300 natural components and identified alantolactone. Data suggested that alantolactone induced activin/SMAD3 signaling in human colon adenocarcinoma HCT-8 cells. The authors also found that alantolactone exhibited antiproliferative function specific to tumor cells, with almost no toxicity to normal cells at a concentration of 5 µg/mL. Furthermore, they proved that the antiproliferative function of alantolactone was activin/SMAD3 dependent. These results suggest that alantolactone performs its antitumor effect by interrupting the interaction between Cripto-1 and the activin receptor type IIA in the activin signaling pathway. Moreover, screening for inhibitors of Cripto-1/ActRII is a potentially beneficial approach to aid in discovering novel cancer treatment.
Journal of Biomolecular Screening 03/2011; 16(5):525-35. · 2.05 Impact Factor
-
Zhen-Bo Song,
Yong-Li Bao,
Yu Zhang,
Xu-Guang Mi,
Ping Wu, Yin Wu,
Chun-Lei Yu,
Ying Sun,
Li-Hua Zheng,
Yan-Xin Huang,
Biao Liu,
Yu-Xin Li
[show abstract]
[hide abstract]
ABSTRACT: TSP50 (testes-specific protease 50) is a testis-specific expression protein, which is expressed abnormally at high levels in breast cancer tissues. This makes it an attractive molecular marker and a potential target for diagnosis and therapy; however, the biological function of TSP50 is still unclear. In the present study, we show that overexpression of TSP50 in CHO (Chinese-hamster ovary) cells markedly increased cell proliferation and colony formation. Mechanistic studies have revealed that TSP50 can enhance the level of TNFα (tumour necrosis factor α)- and PMA-induced NF-κB (nuclear factor κB)-responsive reporter activity, IκB (inhibitor of NF-κB) α degradation and p65 nuclear translocation. In addition, the knockdown of endogenous TSP50 in MDA-MB-231 cells greatly inhibited NF-κB activity. Co-immunoprecipitation studies demonstrated an interaction of TSP50 with the NF-κB-IκBα complex, but not with the IKK (IκB kinase) α/β-IKKγ complex, which suggested that TSP50, as a novel type of protease, promoted the degradation of IκBα proteins by binding to the NF-κB-IκBα complex. Our results also revealed that TSP50 can enhance the expression of NF-κB target genes involved in cell proliferation. Furthermore, overexpression of a dominant-negative IκB mutant that is resistant to proteasome-mediated degradation significantly reversed TSP50-induced cell proliferation, colony formation and tumour formation in nude mice. Taken together, the results of the present study suggest that TSP50 promotes cell proliferation, at least partially, through activation of the NF-κB signalling pathway.
Biochemical Journal 03/2011; 436(2):457-67. · 4.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: SLC5A8 (Solute carrier family 5, member 8), proposed to be a potential tumor suppressor gene, is down-regulated by epigenetic changes in some colorectal cancer cells, and ectopic expression of SLC5A8 in SLC5A8-deficient colon cancer cell lines leads to suppression of the colony-forming ability of these cells. Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to inhibit the proliferation of a variety of tumor (and normal) human cell types. However, the mechanism(s) by which activin A exerts its inhibitory effects are not yet understood. In this study, we showed that activin A up-regulated SLC5A8 expression in colorectal cancer RKO cells and human embryonic kidney (HEK) 293T cells. To elucidate the underlying mechanism involved in this process, we investigated the activation of the Smad signaling pathway, and analyzed the effects of dominant negative Smad3 and Smad2 proteins on activin A-induced SLC5A8 expression. The results indicated that activin A-induced SLC5A8 expression was dependent on activation of Smad3. Further analysis showed that activin A induced SLC5A8 expression via transcriptional activation. Deletion analysis indicated that the CAGA elements located within the -273/-222 region of the human SLC5A8 promoter were responsive to activin A. Taken together, our results strongly suggest that activin A up-regulates SLC5A8 expression through the Smad signaling pathway, which also partially explains the inhibitory effects of activin A in RKO cells.
The international journal of biochemistry & cell biology 12/2010; 42(12):1964-72. · 4.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Earlier studies identified testes-specific protease 50 (TSP50), which encodes a threonine protease, and showed that it was abnormally reactivated in many breast cancer biopsies. Further, it was shown to be negatively regulated by the p53 gene. However, little is known about the biological function of TSP50. In this study, we applied RNA interference to knockdown TSP50 gene expression in P19 murine embryonal carcinoma stem cells and tested whether this modulated the cell phenotype. The results showed that downregulation of TSP50 expression not only reduced cell proliferation, colony formation, and migration but also induced cell apoptosis. Further investigation revealed that knockdown of TSP50 resulted in greater sensitivity to doxorubicin-induced apoptosis and that activation of caspase-3 was involved in this process.
International Union of Biochemistry and Molecular Biology Life 11/2010; 62(11):825-32. · 3.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous studies demonstrated that the expression of testes-specific protease 50 (TSP50) was increased in breast cancer cells and that overexpression of TSP50 can promote tumorigenesis. Thus, it is important to identify the regulatory mechanisms of TSP50 for tumor therapy. In this study, we elucidated the mechanism underlying TSP50 downregulation by basic fibroblast growth factor (bFGF). We used MDA-MB-231 and HEK293T cell lines to address this issue. RT-PCR and promoter activity assays indicated that bFGF downregulates TSP50 expression via transcriptional activation. We next investigated the signaling pathway that mediated the effect of bFGF on TSP50 transcription, and identified that bFGF induced the phosphorylation of ERK and Sp1. An ERK inhibitor suppressed Sp1 phosphorylation and bFGF-reduced TSP50 expression at the mRNA level. In addition, the dominant negative (DN) mutants of ERK and Sp1 both suppressed the reduction of TSP50 by bFGF. Deletion and mutation analyses indicated that the Sp1 site, located within the +237/+239 region of the human TSP50 promoter, is the major responsive element for bFGF. Taken together, our results strongly suggest that bFGF mediates TSP50 downregulation by ERK activation, leading to the phosphorylation of Sp1 in this process.
Journal of Cellular Biochemistry 09/2010; 111(1):75-81. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Butyrate has been shown to display anti-cancer activity through the induction of apoptosis in various cancer cells. However, the underlying mechanism involved in butyrate-induced apoptosis is still not fully understood. Here, we investigated the cytotoxicity mechanism of butyrate in human colon cancer RKO cells. The results showed that butyrate induced a strong growth inhibitory effect against RKO cells. Butyrate also effectively induced apoptosis in RKO cells, which was characterized by DNA fragmentation, nuclear staining of DAPI, and the activation of caspase-9 and caspase-3. The expression of anti-apoptotic protein Bcl-2 decreased, whereas the apoptotic protein Bax increased in a dose-dependent manner during butyrate-induced apoptosis. Moreover, treatment of RKO cells with butyrate induced a sustained activation of the phosphorylation of c-jun N-terminal kinase (JNK) in a dose- and time-dependent manner, and the pharmacological inhibition of JNK MAPK by SP600125 significantly abolished the butyrate-induced apoptosis in RKO cells. These results suggest that butyrate acts on RKO cells via the JNK but not the p38 pathway. Butyrate triggered the caspase apoptotic pathway, indicated by an enhanced Bax-to-Bcl-2 expression ratio and caspase cascade reaction, which was blocked by SP600125. Taken together, our data indicate that butyrate induces apoptosis through JNK MAPK activation in colon cancer RKO cells.
Chemico-biological interactions 03/2010; 185(3):174-81. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The human SLC5A8 gene is a tumor suppressor. Its silencing may contribute to the carcinogenesis and progression of various tumors, which makes this gene an attractive molecular marker and a potential target for diagnosis and therapy. Little is known about transcriptional mechanisms controlling SLC5A8 gene expression. To better understand the molecular mechanisms regulating SLC5A8 expression, we characterized the 5'-regulatory region and a part of exon 1. Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription. Taken together, our results elucidate the mechanism underlying the regulation of SLC5A8 gene transcription and also define a novel regulatory sequence that may be used to increase expression of the SLC5A8 gene in cancer gene therapy.
Cancer genetics and cytogenetics 01/2010; 196(2):124-32. · 1.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Activin, a member of the TGF-beta superfamily, inhibits the proliferation of breast cancer cells. Activin interacts with its type I and type II receptors to induce phosphorylation of intracellular signaling molecules known as Smads. Previous studies showed that mouse ARIP2 can reduce activin signaling by interacting with activin type II receptors (ActRIIs); however, the activity of ARIP2 in breast cancer is still unclear. In this study, we used RT-PCR to obtain a human homologue of mouse ARIP2, human activin receptor-interacting protein 2 (hARIP2). Like murine ARIP2, hARIP2 has a PDZ domain in its NH2-terminal region and can interact specifically with ActRIIs. Overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human breast adenocarcinoma MCF-7 cells and MDA-MB-231 cells. However, down-regulation of hARIP2 expression by RNAi enhanced activin-induced transcriptional activity and reduced cell proliferation and colony formation. Immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant breast tissues such as simple carcinoma, invasive ductal carcinoma and mucinous adenocarcinoma than in benign hyperplasia or fibroadenoma cases. These results suggest that hARIP2 is a putative growth-promoting factor involved in breast tumorigenesis and tumor development.
Cytokine 05/2009; 46(2):251-9. · 3.02 Impact Factor
