TITLE:
Promestriene Affects GREB1 Expression in Estrogen Sensitive Breast Cancer Cells
AUTHORS:
Alvin J. O. Almodovar, Xiang Zhu, Sally A. Litherland, David A. Decker
KEYWORDS:
Breast Cancer, Survivor, Estrogen Receptor Positive, Hormone Therapy, Side Effects, Promestriene
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.9,
August
24,
2015
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.