Differential expression patterns of histone modifying enzymes in ovarian cancer in response to estradiol and bisphenol A (942.3)

Abstract

Ovarian cancer is the ninth most common cancer but the fifth leading cause of cancer death for women. It has long been known that ovarian cancer growth and development is dependent upon estrogen. Conversely there is less known about how environmental estrogens influence ovarian cancer development. Estrogenic compounds have been shown to affect the epigenome, yet little is known about the specific mechanisms by which these changes occur. This work focused on the effects of both estradiol and the endocrine disruptor bisphenol A (BPA) on the expression of histone modifying enzymes (HMEs) in two different human ovarian cancer model systems, SKOV3 and OVCAR3. Specifically, the expression of Set8, a histone methyl transferase, and Sirt1, a histone deacetylase, was examined in response to physiological doses of either estrogen or BPA. In addition, the experiments were carried out using physiological conditions. There are differences in the expression pattern of these genes between the two compounds and also between the two model systems. These results imply that environmental estrogens potentially impact global gene expression by changing the expression of HMEs. Furthermore these changes are different depending on the model system analyzed demonstrating a complex effect of these compounds in human ovarian cancer.