BRM and BRG1 subunits of the SWI/SNF chromatin remodelling complex are downregulated upon progression of benign skin lesions into invasive tumours

• Published in: British journal of dermatology (1951) Vol. 164; no. 6; pp. 1221 - 1227
• Main Authors: Bock, V.L., Lyons, J.G., Huang, X.X.J., Jones, A.M., McDonald, L.A., Scolyer, R.A., Moloney, F.J., Barnetson, R.StC, Halliday, G.M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2011; Wiley-Blackwell
• Subjects: Biological and medical sciences; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Chromatin Assembly and Disassembly - genetics; Dermatology; DNA Helicases; DNA Methylation; Down-Regulation; Humans; Immunohistochemistry; Keratosis, Actinic - genetics; Keratosis, Actinic - metabolism; Medical sciences; Nuclear Proteins; Precancerous Conditions - genetics; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Chromatin; Skin disease; Prognosis; Dermatology; Evolution; Tumor; Subunit
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2011.10267.x

Summary Background  Nonmelanoma skin cancer is caused by exposure to ultraviolet radiation within sunlight. Actinic keratoses (AKs) are benign precursor lesions that can develop into invasive squamous cell carcinoma (SCC). Little is known about the molecular events that lead to human skin cancer progression from benign to invasive. Objectives  To determine novel genes that may be involved in skin cancer progression based on data from an initial microarray screen of human skin cancers. Methods  The SWI/SNF chromatin remodelling ATPase subunit BRM was identified as being downregulated in SCC but not AK compared with normal skin in our microarray screen. Therefore reverse transcription–polymerase chain reaction, gene methylation and protein expression was used to study BRM and its alternative ATPase subunit BRG1 in a range of human skin cancers. Results  We found reduced levels of mRNA coding for BRM but not BRG1 in SCC. BRM mRNA levels in AK were similar to those in normal skin. Deregulation of BRM did not result from hypermethylation of CpG regions in the promoter of these genes. Both BRM and BRG1 protein was reduced by about 10‐fold in 100% of SCC and basal cell carcinoma, but not in AK specimens examined. Conclusions  BRM protein may be decreased due to low levels of mRNA, while BRG1 protein loss appears to be post‐translational. BRM and BRG1 may be novel tumour suppressor genes for human skin cancer. They appear to be involved after development of benign lesions, and are downregulated during progression towards invasion.