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Updated: Jun 12, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
BRG1 expression is increased in human cutaneous melanoma
H Lin1, R P C Wong, M Martinka
1Department of Dermatology and Skin Science, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
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<0·0001). 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.
Insights
BRG1 expression increases in melanoma, driving cancer initiation. Reducing BRG1 in melanoma cells inhibits proliferation by arresting the cell cycle.
Area of Science:
- Oncology
- Cell Biology
- Chromatin Remodeling
Background:
- The SWI/SNF chromatin remodelling complex is crucial for cellular processes and its aberrant expression is linked to cancer.
- While SNF5 is a known tumor suppressor, the role of the catalytic subunit BRG1 in cancer remains unclear.
Purpose of the Study:
- To investigate the role of BRG1 in melanoma development.
- To analyze BRG1 expression in melanocytic lesions and its correlation with clinicopathological variables and patient survival.
Main Methods:
- Tissue microarray and immunohistochemistry were used to evaluate BRG1 expression in dysplastic naevi, primary melanomas, and metastatic melanomas.
- Small interfering RNA was employed to reduce BRG1 expression in melanoma cell lines, followed by cell proliferation and cell cycle assays.
Main Results:
- BRG1 expression was significantly elevated in primary and metastatic melanomas compared to dysplastic naevi.
- BRG1 knockdown in melanoma cells led to reduced proliferation due to G1 phase arrest, with downregulation of cyclin D1.
- No significant correlation was found between BRG1 expression and melanoma patient survival.
Conclusions:
- BRG1 is significantly upregulated in human melanoma.
- Increased BRG1 expression is implicated in melanoma initiation and progression.
- BRG1 plays a role in regulating melanoma cell proliferation.
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