BRG1 expression is increased in human cutaneous melanoma

被引:55
作者
Lin, H. [1 ]
Wong, R. P. C. [1 ]
Martinka, M. [2 ]
Li, G. [1 ]
机构
[1] Univ British Columbia, Vancouver Coastal Hlth Res Inst, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Vancouver Coastal Hlth Res Inst, Dept Pathol, Vancouver, BC V5Z 1M9, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
BRG1; immunohistochemistry; melanoma; tissue microarray; SWI-SNF COMPLEX; CHROMATIN REMODELING COMPLEXES; MAMMALIAN SWI/SNF COMPLEXES; MALIGNANT RHABDOID TUMORS; CYCLIN-DEPENDENT KINASES; CANCER CELL-LINES; HUMAN LUNG-CANCER; INDUCED APOPTOSIS; CD44; EXPRESSION; BREAST-CANCER;
D O I
10.1111/j.1365-2133.2010.09851.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
P>Background 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. Objectives 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. Methods 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. Results We found that BRG1 expression was increased in primary melanoma and metastatic melanoma compared with dysplastic naevi (P < 0 center dot 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. Conclusions Our data indicate that BRG1 is significantly increased in human melanoma and is involved in melanoma initiation.
引用
收藏
页码:502 / 510
页数:9
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