RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Abstract

Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

SHON Is a Novel Estrogen-Regulated Oncogene in Mammary Carcinoma That Predicts Patient Response to Endocrine Therapy

“…Clinically, expression of SHON (32,33). In addition to the classic genomic action associated with nuclear ER, nongenomic ER action has also been reported: cell membrane or cytoplasm-associated ER promotes cellular signaling by direct interaction with a variety of signaling pathways (34).…”

GPER Mediates Activation of HIF1α/VEGF Signaling by Estrogens

“…SkBr3 xenograft tumor growth was evaluated by caliper measurements, along two orthogonal axes: length (L) and width (W). Tumor volumes (in cm 3 ) were estimated by the following formula: TV ¼ L Â (W 2 )/2. At day 40, the animals were sacrificed following the standard protocols and tumors were dissected from the neighboring connective tissue.…”

“…Although the molecular mechanisms involved in breast tumor development remain to be fully understood, it has been established that E2 triggers stimulatory effects by binding to the estrogen receptor (ER)a and ERb that regulate the expression of genes involved in cellcycle progression, cell migration, and survival (2,3). In addition, the G protein-coupled receptor (GPR)30/GPER has been shown to mediate estrogenic signaling in different normal and malignant cell contexts, including breast cancer (3)(4)(5)(6)(7). In this regard, the identification of selective GPER agonists or antagonists (8)(9)(10)(11)(12) has allowed the evaluation of certain biological responses elicited through GPER.…”

Transforming growth factor-β signaling pathway cross-talking with ERα signaling pathway on regulating the growth of uterine leiomyoma activated by phenolic environmental estrogens in vitro

“…TGF-β family members play their roles by binding to cell membrane receptors and by transducing signals. The latter, in turn, is mediated by the phosphorylation of receptor-regulated Smads (R-Smads), which are mainly represented as Smad2 and Smad3 [24]. The UL tissue was found to overexpress TGFBR1, TGFBR2, Smad3, Smad4, and phosphorylated Smad3 compared to the myometrium [25].…”