The SWI/SNF chromatin remodeling complex plays important roles in cellular processes including cell differentiation, cell cycle control, and DNA repairs. Aberrant expression of SWI/SNF subunits is involved in cancer development. The core subunit of 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 analyzed the correlation between BRG1 expression and clinicopathologic variables and patient survival.

Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 48 dysplastic nevi, 90 primary melanomas, and 47 metastatic melanomas. We studied melanoma cell proliferative ability with reduced BRG1 expression by siRNA using cell proliferation assay and cell cycle analysis.

We found that BRG1 expression was increased in primary melanoma and metastatic melanoma compared with dysplastic nevi (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 G1 phase arrest as cyclin D1 is downregulated upon BRG1 knockdown.

Our data indicate that BRG1 is significantly increased in human melanoma and is involved in melanoma initiation.

PMID: 20491765 [PubMed - as supplied by publisher] Source: National Library of Medicine.