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Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma
Author(s) -
Endo Mio,
Yasui Kohichiroh,
Zen Yoh,
Gen Yasuyuki,
Zen Keika,
Tsuji Kazuhiro,
Dohi Osamu,
Mitsuyoshi Hironori,
Tanaka Shinji,
Taniwaki Masafumi,
Nakanuma Yasuni,
Arii Shigeki,
Yoshikawa Toshikazu
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12005
Subject(s) - protein subunit , hepatocellular carcinoma , chromatin , swi/snf , chemistry , chromatin remodeling , microbiology and biotechnology , biology , cancer research , biochemistry , dna , gene
Abstract Background The SWI / SNF chromatin remodelling complex, which contains either brahma‐related gene‐1 ( BRG 1) or brahma ( BRM ) as the catalytic ATP ase, functions as a master regulator of gene expression. Aims To examine alterations of BRG 1 and BRM in hepatocellular carcinoma ( HCC ). Methods We investigated DNA copy number aberrations in human HCC cell lines using a high‐density oligonucleotide microarray. We determined DNA copy numbers and expression levels of BRG 1 and BRM genes in primary HCC tumours, and conducted further searches for mutations in BRG 1 and BRM genes. Results Homozygous deletion of the BRG 1 gene was found in HCC cell line SNU 398. Copy number losses of BRG 1 and BRM genes were observed in 14 (26%) and 7 (13%) of 54 primary HCC tumours respectively. We found four somatic missense mutations in the BRG 1 gene in two of 36 primary HCC tumours, but no mutations in BRM gene. Expression of BRM m RNA , but not BRG 1 m RNA , was significantly reduced in primary HCC tumours, compared to non‐tumour tissue counterparts. Immunohistochemical analyses of non‐tumour liver tissues showed that BRM protein was expressed in hepatocytes and bile‐duct epithelial cells, whereas BRG 1 protein was expressed in bile‐duct epithelial cells, but not in hepatocytes. BRM protein expression was lost in nine (22.5%) of 40 HCC tumours. Loss of BRM protein expression was significantly associated with poor overall survival. Conclusion Reduced expression of BRM may contribute to the carcinogenesis of HCC . Although deletions and mutations in BRG 1 gene were identified, the role of BRG 1 in HCC tumourigenesis remains unclear.