BRG1 expression is increased in human cutaneous melanoma.
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.


OBJECTIVE
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<0·0001). 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.
Lin
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Department of Dermatology and Skin Science, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Wong
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Martinka
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Li
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004265:DNA Helicases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D046228:Microarray Analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases