Histone deacetylase 1 promotes breast cancer progression

Histone deacetylase 1 (HDAC1) promotes breast cancer cellular proliferation by downregulating estrogen receptor-alpha, according to a report in the November 10th International Journal of Cancer.

Loss of estrogen receptor (ER)-alpha expression has been linked to mammary carcinogenesis, breast cancer progression, and breast cancer outcome, the authors explain, but the underlying molecular mechanism for this loss is poorly understood.Because histone deacetylases have been implicated in the alteration of chromatin assembly and tumorigenesis, Dr. Hava Karsenty Avraham and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts explored whether HDAC1 might have a role in regulating ER-alpha function in breast cancer cells.HDAC1 suppressed ER-alpha transcriptional activity in vitro, the authors report, with HDAC1 interacting directly with ER-alpha via the latter’s AF-2 and DBD domains.In cultured breast cancer cells, HDAC1 was associated with ER-alpha, the report indicates, and this association was decreased in the presence of estrogen.Overexpression of HDAC1 in a breast cancer cell line (MCF-7) induced the loss of ER-alpha expression and brought increased proliferation and transformation of breast cancer cells, the researchers note, while treatment with the HDAC1 inhibitor TSA restored ER-alpha expression.”Our findings strongly suggest that HDAC1 affects breast cancer progression by promoting cellular proliferation in association with a reduction in both ER-alpha protein expression and transcriptional activity,” the authors conclude. “Thus, HDAC1 may be a potential target for therapeutic intervention in the treatment of a subset of ER-negative breast cancers.”(Source: Int J Cancer 2003;107:353-358: Reuters Health: November 27, 2003: Oncolink)