The mammalian SWI/SNF chromatin remodeling complex, an essential epigenetic regulator, contains either a single Brm or BRG1 molecule as its catalytic subunit. We observed frequent loss of Brm expression but not of BRG1 in human
gastric cancer cell lines. Treatment with
histone deacetylase inhibitor rescued Brm expression, indicating epigenetic regulation of this gene, and an RNA interference-based colony formation assay revealed antioncogenic properties of Brm. Brm immunostaining of 89 primary
gastric cancers showed an obvious reduction in 60 cases (67%) and a severe decrease in 37 cases (42%). Loss of Brm is frequent in the major
gastric cancer types (well- or moderately-differentiated
tubular adenocarcinoma and poorly-differentiated
adenocarcinoma) and positively correlates with the undifferentiated state. Among the minor
gastric cancer types, Brm expression persists in
signet-ring cell carcinoma and
mucinous adenocarcinoma, but a marked decrease is observed in
papillary adenocarcinoma. Intestinal
metaplasia never shows decreased expression, indicating that Brm is a valid marker of gastric
oncogenesis. In contrast, BRG1 is retained in most cases; a concomitant loss of BRG1 and Brm is rare in
gastric cancer, contrary to other
malignancies. We further show that Brm is required for
villin expression, a definitive marker of intestinal
metaplasia and differentiation. Via regulating such genes important for gut differentiation, Brm should play significant roles in determining the histologic features of gastric
malignancy.