Hyaluronate synthase-2 overexpression alters estrogen dependence and induces histone deacetylase inhibitor-like effects on ER-driven genes in MCF7 breast tumor cells

作者：Vanneste Marion; Hanoux Vincent; Bouakka Mohammed; Bonnamy Pierre Jacques

来源：Molecular and Cellular Endocrinology, 2017, 444(C): 48-58.

DOI：10.1016/j.mce.2017.01.046

• Hyaluronan
• Hyaluronate synthase 2
• Estrogen signaling
• Histone deacetylases
• Breast cancer

In breast carcinoma cells, high levels of hyaluronan (HA) and its CD44 receptor are frequently associated with alteration in estrogen signaling. We demonstrate that stable hyaluronate synthase 2 (HAS2) over expression in estrogen receptor alpha (ER alpha)-positive MCF7 cells oppositely altered estrogen dependence of cell growth and its sensitivity towards antiestrogens. Albeit without effect on Ell alpha expression and estradiol binding properties, HAS2 overexpression increased ER alpha Ser118 phosphorylation as well as transcriptional activity of estrogen in an ERE-luciferase reporter gene assay. However, HAS2 over expression induced partial silencing of E2 driven-genes without affecting the magnitude of regulation by estradiol. This effect was associated with half-reduction in the activity of nuclear histone deacetylases (HDACs) through a post-translational mechanism likely consecutive to the enhanced expression of the histone acetyl-transferase EP300. In conclusion, increase in HA/CD44 interactions may contribute, through an HDAC inhibitor-like and ER-independent mechanism, to the silencing of estrogen driven genes in breast carcinoma.

• 出版日期2017-3-15