title: Estrogen receptors and their implications in colorectal carcinogenesis.
abstract: Upon binding their cognate receptors, ERα (ESR1) and ERβ (ESR2), estrogens activate intracellular signaling cascades that have important consequences for cellular behavior. Historically linked to carcinogenesis in reproductive organs, estrogens have also been implicated in the pathogenesis of different cancer types of non-reproductive tissues including the colon. ERβ is the predominant estrogen receptor expressed in both normal and malignant colonic epithelium. However, during colon cancer progression, ERβ expression is lost, suggesting that estrogen signaling may play a role in disease progression. Estrogens may in fact exert an anti-tumor effect through selective activation of pro-apoptotic signaling mediated by ERβ, inhibition of inflammatory signals and modulation of the tumor microenvironment. In this review, we analyze the estrogen pathway as a possible therapeutic avenue in colorectal cancer, we report the most recent experimental evidence to explain the cellular and molecular mechanisms of estrogen-mediated protection against colorectal tumorigenesis, and we discuss future challenges and potential avenues for targeted therapy.
authors.affiliation: Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College , Dublin , Ireland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caiazza
authors.affiliation: Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College , Dublin , Ireland.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ryan
authors.affiliation: Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College , Dublin , Ireland.
authors.forename: Glen
authors.initials: G
authors.lastname: Doherty
authors.affiliation: Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; Department of Surgery, St. Vincent's University Hospital, Elm Park , Dublin , Ireland.
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
authors.affiliation: Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College , Dublin , Ireland ; Department of Pathology, Saint Vincent's University Hospital , Dublin , Ireland.
authors.forename: Kieran
authors.initials: K
authors.lastname: Sheahan
keywords: colorectal cancer; estrogen; estrogen receptor; tumor immunology; tumor microenvironment