Hormonal control of breast cancer metastasis

Breast cancer is hormone-dependent and sex steroids, particularly estrogen and progesterone, have a central role in the development and progression of the disease. Prolonged exposure to estrogen and/or progesterone is a risk factor for breast cancer carcinogenesis, even if the effects of sex steroids on breast cancer metastasis are open to discussion. Emerging evidence suggests that sex steroids participate in extranuclear signaling in addition to genomic functions. In this review, we summarize the current knowledge of sex steroid biological actions on breast cancer cells. Estrogen and progesterone rapidly determine actin cytoskeleton reorganization in breast cancer cells, through the regulation of actin-binding proteins: this causes the formation of membrane structures facilitating breast cancer cell migration and invasion. Moreover, steroid receptors interact and transactivate receptor tyrosine kinases (as well as epidermal growth factor receptor and insulin-like growth factor receptor), resulting in growth factor-like effects that favor cancer cell invasion. In addition, the expression of metastasis-associated molecules, such as E-cadherin, matrix metallo-proteinases, growth factors, chemokines and their receptors, are regulated by sex steroids, causing the epithelial-tomesenchymal- like transition. However, it has been also demonstrated that sex steroids and their receptors protect against breast cancer cell invasiveness through distinct mechanisms. Nowadays , the molecular basis of breast cancer progression to metastasis and the role of estrogen receptor (ER) and progesterone receptor (PR) signaling remain poorly understood. Therefore, the understanding of the effects of steroids in this process is decisive and may turn out to be of relevance for clinical purposes in the future. © Copyright 2013, CIC Edizioni Internazionali, Roma.