-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Mutation of BRAF is a prevalent event in melanoma. Despite much attention to the role of BRAF mutation in melanoma, the status of BRAF protein expression and its significance in melanoma progression is unknown. OBJECTIVES: We investigated BRAF expression level in different stages of melanocytic lesions and evaluated its correlation with clinicopatholigical features and patient survival. METHODS: Using tissue microarray, BRAF expression and its correlation with patient outcome was evaluated in 49 nevi samples and 370 melanoma patients. We also evaluated the correlation of BRAF protein expression and V600E mutation using direct sequencing. RESULTS: Compared with nevi samples, BRAF expression was remarkably increased in primary melanomas and further increased in metastatic melanomas (P=1.8×10(-11) ). High BRAF expression was significantly correlated with thicker tumors, ulceration and higher American Joint Committee on Cancer (AJCC) stages (P=1.5×10(-7) , 1.5×10(-5) , 3.6×10(-13) , respectively). In primary melanoma cases, patients with high BRAF expression had significantly worse overall (P=0.009) and disease-specific five-year survival (P=0.007). While there was a trend for higher prevalence of BRAF-V600E mutation in patients with high BRAF protein expression, no significant correlation was observed between protein expression and BRAF mutation. Furthermore, univariate Cox-regression analysis confirmed high BRAF protein expression as a strong risk factor for poor patient survival in primary melanoma (HR2.08 overall survival; HR2.39 disease-specific survival). CONCLUSION: Our data demonstrated that BRAF protein expression is significantly increased during melanoma progression. In addition, we revealed a novel prognostic value for BRAF protein expression in primary melanoma as it is significantly correlated with poor patient survival.
British Journal of Dermatology 04/2013; · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We previously reported reduced expression of Sox4 in metastatic melanoma and its role in suppression of cell migration and invasion through inhibition of nuclear factor (NF)-κB p50. Sox4 can also bind to the promoter sequence of Dicer, a microRNA (miRNA) biogenesis factor. Interestingly, altered expression of Dicer was also observed in cancers. However, the potential mechanisms that regulate Dicer expression and its potential significance in melanoma progression are unknown. Here, we studied the regulation of Dicer expression by Sox4 and its role in suppression of melanoma invasion. Our data showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least twofold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown. Furthermore, we examined the expression of Dicer protein in a large set of melanocytic lesions (n=514) at different stages by tissue microarray and found that Dicer expression is inversely correlated with melanoma progression (P<0.0001). Consistently, reduced Dicer expression was correlated with a poorer overall and disease-specific 5-year survival of patients (P=0.015 and 0.0029, respectively). In addition, we found a significant correlation between expression of Sox4 and Dicer proteins in melanoma biopsies (P=0.009), further indicating the regulation of Dicer expression by Sox4. Finally, we revealed that knockdown of Sox4 induces a major change in the expression pattern of miRNAs in melanoma cells, mainly due to reduced expression of Dicer. Our results pinpoint the regulation of Dicer expression by Sox4 in melanoma and the critical role of Dicer in suppression of melanoma invasion. Our findings on Sox4-regulated miRNA biogenesis pathway may aid toward the development of novel targeted therapeutic approaches for melanoma.Oncogene advance online publication, 11 June 2012; doi:10.1038/onc.2012.239.
Oncogene 06/2012; · 6.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The electro-optical properties of the PMN-xPT single-crystal relaxor solid solutions with different PT contents (x = 6, 10, 13%) and the PLMN-25PT transparent ceramic with a La content of 3%, which has been synthesized for the first time,
have been studied at room temperature. It has been shown that the dependence of the quadratic electro-optical coefficients
on the PT concentration in single crystals passes through a maximum at x ∼ 13%. It has been revealed that, although the PT concentration in the PLMN-25PT ceramic is above 13%, this material exhibits
the largest quadratic electro-optical coefficients and the lowest half-wave voltage among all the known relaxor systems. Possible
origins of the above phenomena have been discussed.
Physics of the Solid State 04/2012; 52(10):2142-2146. · 0.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein kinase involved in cell-extracellular matrix interactions, cytoskeletal organization and cell signaling. Overexpression of ILK in epithelial cells leads to anchorage-independent growth with increased cell cycle progression. Previously, we have shown that ILK upregulation strongly correlates with melanoma progression, invasion and inversely correlates with 5-year survival of melanoma patients. However, the molecular mechanism by which ILK enhances melanoma progression is currently unknown. In the present study, we found that proangiogenic molecule interleukin-6 (IL-6) is the downstream target of ILK in melanoma cells. ILK overexpression increased IL-6, whereas silencing of ILK suppressed IL-6 expression at both messenger RNA and protein levels. ILK also altered the activity and subcellular localization of nuclear factor-kappaB (NF-κB) subunit p65. We further found that ILK enhanced the IL-6 gene transcription by promoting the binding of NF-κB p65 to IL-6 promoter. Moreover, ILK overexpression in melanoma cells enhanced the tube-forming ability of endothelial cells in vitro and microvessel formation in vivo. ILK-induced tube and blood vessel formation of endothelial cells was significantly reduced upon IL-6 inhibition in ILK-overexpressing melanoma cells. To delineate the mechanism by which ILK-induced IL-6 production can enhance angiogenesis, further analysis of the downstream targets of IL-6 signaling showed an increased activity of the signal transducer and activator of transcription 3 (STAT3) in ILK-overexpressing cells. As STAT3 binds to vascular endothelial growth factor (VEGF) promoter, we found that VEGF levels were elevated in ILK-overexpressing cells and declined upon transfection of IL-6 small interfering RNA, suggesting that ILK may regulate VEGF expression through IL-6 pathway by activating STAT3.
Oncogene 01/2011; 30(24):2778-88. · 6.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Breast cancer metastasis suppressor 1 (BRMS1) has been reported to suppress metastasis without significantly affecting tumorigenicity in breast cancer and ovarian cancer. To investigate the role of BRMS1 in human melanoma progression and prognosis, we established tissue microarray and BRMS1 expression was evaluated by immunohistochemistry in 41 dysplastic nevi, 90 primary melanomas and 47 melanoma metastases. We found that BRMS1 expression was significantly decreased in metastatic melanoma compared with primary melanoma or dysplastic nevi (P=0.021 and 0.001, respectively, χ(2) test). In addition, reduced BRMS1 staining was significantly correlated with American Joint Committee on Cancer stages (P=0.011, χ(2) test), but not associated with tumor thickness, tumor ulceration and other clinicopathological parameters. Furthermore, BRMS1 expression was significantly correlated with disease-specific 5-year survival of melanoma patients (P=0.007, log-rank test). Multivariate Cox regression analysis revealed that BRMS1 staining was an independent prognostic factor for melanoma patients (relative risk=0.51; confidence interval=0.29-0.91; P=0.022). Moreover, we demonstrated that BRMS1 overexpression inhibited endothelial cell growth and tube formation ability by suppressing NF-κB activity and IL-6 expression in vitro. We also showed that knockdown of BRMS1 increased IL-6 expression and promoted endothelial cell growth and tube formation. In addition, our data revealed that the BRMS1-mediated IL-6 expression is dependent on NF-κB. Strikingly, our in vivo studies using nude mice confirmed that BRMS1 inhibited blood vessel formation and the recruitment of CD31-positive cells in matrigel plugs. Taken together, BRMS1 expression was decreased in metastatic melanomas, which resulted in deficient suppression of angiogenesis and contributed to melanoma progression. BRMS1 may serve an important prognostic marker and therapeutic target for melanoma patients.
Oncogene 10/2010; 30(8):896-906. · 6.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The SWI/SNF chromatin remodelling complex plays important roles in cellular processes including cell differentiation, cell cycle control and DNA repair. Aberrant expression of SWI/SNF subunits is involved in cancer development. The core subunit of the SWI/SNF complex, SNF5, has been shown to be inactivated in malignant rhabdoid tumours and has been defined as a tumour suppressor. However, the role of the catalytic subunit, BRG1, is not well defined in cancer.
To investigate the role of BRG1 in melanoma development, we examined the expression of BRG1 in melanocytic lesions at different stages and analysed the correlation between BRG1 expression and clinicopathological variables and patient survival.
Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 48 dysplastic naevi, 90 primary melanomas and 47 metastatic melanomas. We studied melanoma cell proliferative ability with reduced BRG1 expression by small interfering RNA using cell proliferation assay and cell cycle analysis.
We found that BRG1 expression was increased in primary melanoma and metastatic melanoma compared with dysplastic naevi (P<0·0001). We did not find any correlation between BRG1 expression and melanoma patient survival. In addition, we demonstrated that knockdown of BRG1 in melanoma cell lines resulted in significantly reduced cell proliferative ability. This reduced cell proliferation is due to G(1) phase arrest as cyclin D(1) is downregulated upon BRG1 knockdown.
Our data indicate that BRG1 is significantly increased in human melanoma and is involved in melanoma initiation.
British Journal of Dermatology 09/2010; 163(3):502-10. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The inhibitor of growth family member 3 (ING3) has been shown to modulate transcription, cell cycle control and apoptosis. We previously reported that nuclear ING3 expression was remarkably reduced in melanomas, which correlated with a poorer patient survival, suggesting that decreased ING3 expression may be associated with melanoma progression. However, the mechanism of diminished ING3 expression in melanoma is not clear. Here we show that ING3 level was decreased in metastatic melanoma cells because of a rapid degradation. Furthermore, we showed that ING3 undergoes degradation through the ubiquitin-proteasome pathway. ING3 physically interacts with subunits of E3 ligase Skp1-Cullin-F-box protein complex (SCF complex). Knockdown of F-box protein S-phase kinase-associated protein 2 (Skp2) reduces the ubiquitination of ING3 and significantly stabilizes ING3 in melanoma cells. In addition, lysine 96 residue is essential for ING3 ubiquitination as its mutation to arginine dramatically abrogated ING3 degradation. Disruption of ING3 degradation stimulated ING3-induced G1 cell-cycle arrest and enhanced ultraviolet-induced apoptosis. Taken together, our data show that ING3 is degraded by the ubiquitin-proteasome pathway through the SCF(Skp2) complex and interruption of ING3 degradation enhances the tumor-suppressive function of ING3, which provides a potential cancer therapeutic approach by interfering ING3 degradation.
Oncogene 11/2009; 29(10):1498-508. · 6.37 Impact Factor
-
J Bai,
J Zhang,
J Wu,
L Shen,
J Zeng,
J Ding,
Y Wu,
Z Gong,
A Li,
S Xu,
J Zhou, G Li
[show abstract]
[hide abstract]
ABSTRACT: JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As(2)O(3)) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As(2)O(3) on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin alpha(V)beta(3) signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.
Oncogene 11/2009; 29(8):1227-37. · 6.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BH3-only proteins are a subset of the Bcl-2 family of apoptotic regulators. BH3-only proteins function as 'damage sensors' in the cell; they are activated in response to cellular stress or DNA damage, whereupon they initiate apoptosis. Apoptosis is the primary mechanism by which the body rids itself of genetically defective cells and is critical for preventing the accumulation of cells with tumorigenic potential. Therefore, dysregulation of BH3-only proteins may promote tumorigenesis. Furthermore, functional apoptosis pathways are required for the success of most cancer treatments, including chemotherapy. Resistance to chemotherapy, as seen with malignant melanoma, often reflects an inability of tumor cells to undergo apoptosis. By deciphering the roles of BH3-only proteins in tumorigenesis, we may learn how to manipulate cell death pathways to overcome apoptotic resistance. This review summarizes the current knowledge of BH3-only proteins and how they contribute to tumorigenesis, with particular attention given to studies involving melanoma.
Cellular and Molecular Life Sciences CMLS 03/2007; 64(3):318-30. · 6.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P < 0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P > 0.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development.
British Journal of Cancer 07/2006; 95(1):80-6. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: p53, a commonly mutated gene in human cancers, participates in cell cycle arrest, DNA repair and apoptosis. A small pharmacological compound, CP-31398, was found to have the ability to promote proper p53 protein folding, activate p53 transcription of downstream targets, and slow tumour growth in mice. Additionally, CP-31398 was found to be able to convert mutant p53 to wild-type conformation in several cell lines.
To examine if CP-31398 can revert all mutant p53 proteins to wild-type function.
We studied a series of apoptotic responses to CP-31398 in three melanoma cell lines varying in p53 mutation status.
Upon a moderate dose of CP-31398 treatment (15 microg mL(-1)), only the wild-type p53 MMRU and the single p53 point mutation MeWo cells exhibited apoptosis. Another melanoma cell line, Sk-mel-110, containing multiple p53 mutations, did not exhibit apoptosis. Although CP-31398 enhanced overall p53 protein level, its ability to promote proper folding of p53 protein was limited to CP-31398-sensitive MMRU and MeWo cells. These sensitive cells showed an increased Bax and PUMA transcription, altered mitochondrial membrane potential, followed by the release of cytochrome c, and cleaved caspase-9 and caspase-3. We also demonstrated that Apaf-1 was not involved in CP-31398-mediated apoptosis.
Our results suggest that the ability of CP-31398 to revert mutant p53 proteins to wild-type conformation may be correlated to p53 mutational status. More studies are necessary, to further investigate the effect of CP-31398 on mutant p53 and its potential applications as an anticancer agent.
British Journal of Dermatology 12/2005; 153(5):900-10. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Early studies of the inhibitor of growth 1 ( ING1) gene, the founding member of the ING tumor suppressor family, demonstrated that this gene plays an important role in apoptosis and cellular senescence. Four other related genes have since been identified and found to be involved in various biological activities, including cell cycle arrest, regulation of gene transcription, DNA repair and apoptosis. The biochemical functions of ING proteins as histone acetyltransferases and histone deacetylase co-factors ties this new tumor suppressor family to the regulation of transcription, cell cycle check-points, DNA repair and apoptosis. This review is aimed at summarizing the known biological functions of the ING tumor suppressors and the signalling pathways that they involve.
Cellular and Molecular Life Sciences CMLS 11/2004; 61(19-20):2597-613. · 6.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Malignant melanoma is a life-threatening skin cancer due to its highly metastatic character and resistance to radio- and chemotherapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. p53, the most frequently mutated tumour suppressor gene in human cancers, is a key apoptosis inducer. However, p53 mutation is only found in 15-20% of melanoma biopsies. Recently, it was found that Apaf-1, a downstream target of p53, is inactivated in metastatic melanoma. Specifically, loss of heterozygosity (LOH) of the Apaf-1 gene was found in 40% of metastatic melanoma. To determine if loss of Apaf-1 expression is indeed involved in melanoma progression, we employed the tissue microarray technology and examined Apaf-1 expression in 70 human primary malignant melanoma biopsies by immunohistochemistry. Our data showed that Apaf-1 expression is significantly reduced in melanoma cells compared with normal nevi (chi(2)=6.02, P=0.014). Our results also revealed that loss of Apaf-1 was not associated with the tumour thickness, ulceration or subtype, patient's gender, age and 5-year survival. In addition, our in vitro apoptosis assay revealed that overexpression of Apaf-1 can sensitise melanoma cells to anticancer drug treatment. Taken together, our data indicate that Apaf-1 expression is significantly reduced in human melanoma and that Apaf-1 may serve as a therapeutic target in melanoma.
British Journal of Cancer 10/2004; 91(6):1089-95. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epidemiological evidence indicates that exposure to ultraviolet (UV) radiation is directly linked to the increase of both incidence and mortality of melanoma. However, the genetic changes caused by UV radiation that lead to melanoma formation remain poorly understood. Recently, a potential tumour suppressor gene ING1 (inhibitor of growth 1) was shown to inhibit cell growth and induce apoptosis in the presence of p53. We have demonstrated that the expression of ING1 is induced after UV irradiation and that ING1 enhances the repair of UV-damaged DNA.
To investigate if ING1 plays a role in melanoma formation.
We examined p33ING1 expression levels in 14 melanoma cell lines.
We found that p33ING1 is overexpressed at both mRNA and protein levels in melanoma cell lines compared with normal melanocytes. Single-strand conformation polymorphism (SSCP) analysis showed band shifting in two melanoma cell lines. DNA sequencing confirmed that there were nucleotide alterations in the ING1 gene in Sk-mel-24 and Sk-mel-110 cell lines. Two silent nucleotide alterations in exon 1a were detected in Sk-mel-110. In Sk-mel-24, the A-->G nucleotide alteration at codon 260 resulted in an amino acid change from Asn to Ser, while seven other nucleotide alterations were silent. To determine if the silent nucleotide alterations in these two melanoma cell lines were due to polymorphism, SSCP analysis of ING1 gene was performed in 25 healthy volunteers. No band shift was observed in the SSCP analysis, suggesting that the nucleotide alterations in the melanoma cell lines are unlikely to be due to polymorphism.
Taken together, our data demonstrate that ING1 is overexpressed, but infrequently mutated, in melanoma cell lines.
British Journal of Dermatology 04/2002; 146(4):574-80. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.
Experimental Cell Research 01/2002; 271(2):305-14. · 3.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The biological functions of the tumor suppressor, ING1, have been studied extensively in the last 5 years since it was cloned. It shares many biological functions with those of p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, and chemosensitivity. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. In this study, we report that p33(ING1) (one of ING1 isoforms) is also involved in the modulation of DNA repair. We found that overexpression of p33(ING1) enhances repair of UV-damaged DNA and that p53 is required for the repair process. Furthermore, binding between ING1 and GADD45 has been detected. These observations suggest that p33(ING1) cooperates with p53 in nucleotide excision repair and that GADD45 may be one of its components.
Cancer Research 08/2001; 61(13):4974-7. · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cutaneous malignant melanoma is a life-threatening cancer with poor prognosis due to a high metastasis potential. The main obstacle in treatment of metastatic melanoma is the resistance to chemotherapy. Recent studies indicated that apoptosis is a common mechanism of action for various cytotoxic agents. As p53 plays an important part in apoptosis, we investigated the role of p53 in chemosensitivity of melanoma cells. Previously, we found that melanoma cell lines containing wild-type p53 have significantly higher response rates to chemotherapy than cell lines with a mutant p53 gene. To confirm the role of p53 in melanoma chemosensitivity further, we transfected an expression vector, pED1, which carries a mutant p53 gene, into a wild-type p53 melanoma cell line, MMAN. We examined the effect of mutant p53 on camptothecin-induced apoptosis and the expression of genes which are known to be involved in apoptosis or drug resistance, such as bcl-2, bax, bak, p21waf1, and P-glycoprotein. Our results indicate that overexpression of the mutant p53 increased the growth rate of MMAN cells, reduced the sensitivity to camptothecin, and lowered drug-induced apoptosis by 2-3-fold. Flow cytometry indicated that the camptothecin-induced apoptosis is not associated with G1 arrest. Furthermore, camptothecin treatment reduced bcl-2 and P-glycoprotein expression in wild-type p53 MMAN cells, but not cells overexpressing mutant p53. These results demonstrate that p53 mutational status is a determinant of melanoma chemosensitivity. p53 may downregulate bcl-2 and P-glycoprotein to induce apoptosis in melanoma cells after chemotherapy.
Journal of Investigative Dermatology 04/2000; 114(3):514-9. · 6.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Skin cancer is extremely common. Epidemiological studies indicated that ultraviolet radiation (UV) is the primary cause for skin cancers, and that retinoic acid (RA) is able to inhibit this UV-induced skin carcinogenesis; however, the molecular mechanism of the anti-UV action of RA is unclear.
The purpose of this study is to investigate if RA enhances the removal of UV-induced DNA damage.
The effect of RA on UV-induced apoptosis and DNA repair was investigated by ELISA apoptosis assay and CAT assay.
Both all-trans-RA and 9-cis-RA did not promote UV-induced apoptosis nor the repair of UV-damaged DNA in human keratinocytes. Furthermore, RA did not induce the expression of p53.
The inhibition of RA on skin carcinogenesis is not due to enhanced removal of UV-damaged DNA. Therefore, RA does not inhibit skin cancer development at the initiation stage, but possibly at the promotion and progression stages.
Journal of Cutaneous Maedicine and Surgery 02/2000; 4(1):2-7. · 0.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The tumour suppressor, p53, is recognized as a crucial molecule in regulating cellular responses to various DNA-damaging agents. Very early on in the development of nonmelanoma cancers p53 is mutated or lost, suggesting that p53 is crucial in protecting normal keratinocytes from the harmful effects of ultraviolet (UV) radiation.
Using two mouse models, one with multiple copies of mutant p53 and the other a p53 "knockout," our laboratory has examined a role for p53 in UV-induced DNA damage and determined if these effects are differentiation dependent.
We outline in this review a proposed model reflecting differentiation-dependent p53 regulation of UV-induced responses in keratinocytes. After exposure to UV, basal keratinocytes repair damaged DNA, whereas differentiating keratinocytes undergo cell death, both processes are regulated by p53.
Journal of Cutaneous Maedicine and Surgery 08/1999; 3(5):280-3. · 0.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To find out the relation between personality factors of edentulous patients and the degree of their satisfaction to the complete dentures.
Under the condition of controlling quality of complete dentures, 165 subjects were investigated by using the patient denture satisfaction questionnaire and the revised Cattell's 16 personality factors questionnaire after wearing the complete dentures for one and three months.
The personality factors of edentulous patients such as conscientiousness (G factor), shrewdness (N factor) and so on do affect their denture satisfaction in every aspect of the dentures.
The oral prosthodontists not only need improving technological quality of prostheses but also need paying attention to patients' psychological characteristics.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 06/1999; 34(3):184-6.
