title: 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 to be a major contributing factor in the malignancy of breast cells. Targeting the ER signaling pathway has been a focal point in the development of breast cancer therapy. Although approximately 75 % of breast cancer patients are classified as luminal type (ER(+)), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrine-based 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.
authors.affiliation: Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Joe X
authors.initials: JX
authors.lastname: Qiao
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Cancer Institute, Suite 2.6C, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Cancer Institute, Suite 2.6C, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
authors.forename: George
authors.initials: G
authors.lastname: Wu
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Cancer Institute, Suite 2.6C, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Cancer Institute, Suite 2.6C, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
keywords: Breast cancer; Crosstalk; ER-α; Growth factor; KLF4; TGF-β; Ubiquitination; estrogen