Abstract
Promestriene (3-propyl ethyl, 17B-methyl estradiol) is a synthetic estrogen analogue with reported minimal systemic absorption which has been suggested for topical treatment of vaginal atrophy. Promestriene’s ability to stimulate proliferation and estrogen responsive gene expression was analyzed in estrogen receptor (ER+) positive breast cancer cell lines MCF-7, T-47D, and BT-474 using CFSE flow cytometric analysis, and quantitative RT-PCR analysis of GREB1 RNA expression, an estrogen responsive gene involved in estrogen receptor alpha expression. In estrogen replete conditions, Promestriene did not stimulate proliferation even at high concentrations (100,000 pg/ml). However, anti-estradiol depletion allowed low dose Promestriene (2 - 10 pg/ml) to stimulate GREB1 expression in all three cell lines at levels equal to that induced by estradiol (BT-474) or significantly higher than estradiol (MCF7 and T-47D). These findings suggest that Promestriene has the potential to support estrogen like cell signaling, a possible contraindication for use in treatment of vaginal atrophy associated with breast cancer aromatase inhibitor therapy.
Highlights
IntroductionThe majority of breast cancer cases (70% - 80%) in the United States are reported as being hormone receptor positive (HR+), meaning that they express estrogen receptors (ER) or progesterone receptors (PR) or both [1]
The National Cancer Institute of the National Institutes of Health 2015 report estimates life time risk for breast cancer for women in the United States at 12.3% [1]
For BT-474 cells, there was no significant difference in the GREB1 expression stimulated by 2 pg/ml Promestriene compared to that induced by estradiol in either estrogen-replete or depleted conditions (Figure 2(b))
Summary
The majority of breast cancer cases (70% - 80%) in the United States are reported as being hormone receptor positive (HR+), meaning that they express estrogen receptors (ER) or progesterone receptors (PR) or both [1]. (2015) Promestriene Affects GREB1 Expression in Estrogen Sensitive Breast Cancer Cells. In breast cancer oncology, the discovery of breast cancer growth stimulation through ovarian hormones indicated the expression of estrogen receptors (ER) by tumor cells as a target for directed anti-hormone therapies. A problem arising from chronic exposure to anti-hormone therapies is side effects of estrogen deprivation including symptoms similar to those seen in menopausal women such as thinning and shrinking of vaginal and breast tissues, vaginal dryness, soreness, painful intercourse and urinary incontinence [6]-[8]. Topical application of Promestriene has been suggested as a possible treatment for reducing such symptoms
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