Abstract
When women reach menopause, they face dramatic changes which can include severe symptoms such as night sweats, vaginal dryness, depression, hot flashes, and osteoporosis. These symptoms can be treated by hormone therapy consisting of estrogen and progesterone, but this combined therapy is associated with an increase in the risk of breast cancer; thus another approach for control of menopausal symptoms is desirable. Selective Estrogen Receptor Modulators (SERMs) are used for reducing breast tumor incidence as well as increasing bone mineral density (BMD). Clinical studies showed that a combination of SERM and one or more estrogens can increase BMD, and relieve menopausal symptoms. This combination is referred to as a Tissue Selective Estrogen Complex (TSEC). As a TSEC, the combination of the SERM, bazedoxifene (BAZ) and conjugated estrogens (CE) inhibited MCF-7 breast cancer cell growth in vitro. I tested the level of progesterone receptor (PR) activity using a GRE-e1b-luc reporter gene which generates luciferase when the receptor is activated. I optimized the concentration of PR and the level of progesterone in dose response experiments. In HeLa cells transfected only with PR and the luciferase reporter gene, PR activity was not stimulated by CE, BAZ or BAZ/CE. On the other hand, in progesterone-treated cells expressing both PR and ER (estrogen receptor), BAZ and BAZ/CE stimulated PR activity while CE inhibited the receptor’s transcriptional activity.
