Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Abstract

Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

“…The effect of these hormones on EMT [27][28][29] is known; however, the mechanism(s) through which estrogens promote this process remain unclear. We were able to demonstrate that estrogen promotes TJ disruption, HER2 Fig.…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…The presence of ERα is a favorable prognostic marker associated with less invasive tumors, whereas tissues that are negative for ERα tend to be more aggressive. Introduction of ERα into ERα-negative breast cancer cells attenuates the aggressive cancerous phenotype in vitro [92,93]. Deregulation of ERα-coregulator signaling can lead to the aberrant expression of Snail resulting in the loss of expression of E-cadherin and invasive growth.…”

FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

“…Estrogen signaling pathways are involved in the growth and development of breast tumors through the activation of estrogen receptor alpha (ERα) [1]. Most breast cancers express high levels of ERα and exhibit estrogen-dependent proliferation.…”