Abstract
Sex hormones play important roles in the onset and progression of several cancers, such as breast, ovarian, and prostate cancer. Although drugs targeting sex hormone function are useful in treating cancer, tumors often develop resistance. Thus, we need to define the downstream effectors of sex hormones in order to develop new treatment strategies for these cancers. Recent studies unearthed one potential mediator of steroid hormone action in tumors: growth regulation by estrogen in breast cancer 1 (GREB1). GREB1 is an early estrogen-responsive gene, and its expression is correlated with estrogen levels in breast cancer patients. Additionally, GREB1 responds to androgen in prostate cancer cells, and can stimulate the proliferation of breast, ovarian, and prostate cancer cells. Recent studies have shown that GREB1 also responds to progesterone in human endometrial cells, suggesting that GREB1 is a pan steroid-responsive gene. This mini-review examines evidence that GREB1 participates in several hormone-dependent cancers and could be targeted to treat these cancers.
Highlights
Steroid hormones are a selective branch of signaling molecules, which are biosynthesized from cholesterol derivatives in the mitochondria [1]
We found that GREB1 is transcriptionally activated by steroid receptor coactivator (SRC)-2 via the progesterone–progesterone receptors (PRs) axis in endometrium [40], and a novel fusion gene, GREB1-SRC-2, was detected in uterine sarcoma [41]
GREB1a is the full-length isoform, whereas variant splicing and the introduction of early termination codons result in GREB1b and GREB1c, which terminate after exons ind1ep0eanndden9,tlryesepnehcatnivceelyth[e4e6x] p(Freigssuiroen2o).f estrogen receptors (ERs) target genes PS2 and SDF1, while exogenously expressed GREB1b had no effect [46]
Summary
Steroid hormones are a selective branch of signaling molecules, which are biosynthesized from cholesterol derivatives in the mitochondria [1]. Hormones in the sex steroid class (i.e., estrogen, progesterone, and androgen) are vital for the development and maintenance of sexual characteristics as well as for general reproductive function [2]. Sex-steroid hormones exert their physiologic and pathological function through their cognate receptors (steroid receptors), including estrogen receptors (ERs), androgen receptors (ARs), and progesterone receptors (PRs). All of these receptors belong to the nuclear receptor superfamily and consist of tissue-specific subtypes [3,4]. Overcoming this challenge will require defining the mechanisms by which hormones drive these cancers and identifying new therapeutic targets
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