Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers. Export

@article{citeulike:1318233, abstract = {Estrogen exposure is considered a significant risk factor for breast cancer development. Estrogen receptor (ER) alpha is expressed at low levels in normal epithelia, and its expression is dramatically up-regulated as transformation progresses during mammary hyperplasia and adenocarcinoma development. The mechanism(s) driving ERalpha up-regulation during mammary tumorigenesis remains unclear. Caveolin-1 (Cav-1) is the structural protein of plasmalemmal invaginations, termed caveolae, which functions as a tumor suppressor gene. Interestingly, Cav-1 dominant-negative mutations are exclusively found in ERalpha-positive breast cancer samples. In support of these clinical findings, ERalpha expression is increased in Cav-1 (-/-) null mammary epithelia, and estrogen stimulation further enhances the growth of Cav-1-deficient three-dimensional epithelial structures. These phenotypes correlate with augmented levels of cyclin D1. In addition, Cav-1 gene inactivation induces the accumulation of a cell population with the characteristics of adult mammary stem cells. Primary cultures of Cav-1 (-/-) mammary epithelial cells exhibit premalignant changes, such as abnormal lumen formation, epidermal growth factor-independent growth, defects in cell substrate attachment, and increased cell invasiveness. Thus, Cav-1 gene inactivation promotes premalignant alterations in mammary epithelia and induces increased ERalpha expression levels and the up-regulation of cyclin D1. As tumor formation is a multihit process, Cav-1 mutations that occur during the early stages of mammary transformation may be a critical upstream/initiating event leading to increased ERalpha levels.}, address = {Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.}, author = {Sotgia, F. and Rui, H. and Bonuccelli, G. and Mercier, I. and Pestell, R. G. and Lisanti, M. P.}, citeulike-article-id = {1318233}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-06-2805}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17108100}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17108100}, day = {15}, doi = {10.1158/0008-5472.CAN-06-2805}, issn = {0008-5472}, journal = {Cancer Res}, keywords = {breast, cancer, caveolin-1, cyclin, stem\_cell, tumor}, month = {November}, number = {22}, pages = {10647--10651}, posted-at = {2007-05-21 21:41:19}, priority = {3}, title = {Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-06-2805}, volume = {66}, year = {2006} }

TY - JOUR ID - citeulike:1318233 L3 - citeulike-article-id:1318233 N2 - Estrogen exposure is considered a significant risk factor for breast cancer development. Estrogen receptor (ER) alpha is expressed at low levels in normal epithelia, and its expression is dramatically up-regulated as transformation progresses during mammary hyperplasia and adenocarcinoma development. The mechanism(s) driving ERalpha up-regulation during mammary tumorigenesis remains unclear. Caveolin-1 (Cav-1) is the structural protein of plasmalemmal invaginations, termed caveolae, which functions as a tumor suppressor gene. Interestingly, Cav-1 dominant-negative mutations are exclusively found in ERalpha-positive breast cancer samples. In support of these clinical findings, ERalpha expression is increased in Cav-1 (-/-) null mammary epithelia, and estrogen stimulation further enhances the growth of Cav-1-deficient three-dimensional epithelial structures. These phenotypes correlate with augmented levels of cyclin D1. In addition, Cav-1 gene inactivation induces the accumulation of a cell population with the characteristics of adult mammary stem cells. Primary cultures of Cav-1 (-/-) mammary epithelial cells exhibit premalignant changes, such as abnormal lumen formation, epidermal growth factor-independent growth, defects in cell substrate attachment, and increased cell invasiveness. Thus, Cav-1 gene inactivation promotes premalignant alterations in mammary epithelia and induces increased ERalpha expression levels and the up-regulation of cyclin D1. As tumor formation is a multihit process, Cav-1 mutations that occur during the early stages of mammary transformation may be a critical upstream/initiating event leading to increased ERalpha levels. IS - 22 JF - Cancer Res SN - 0008-5472 AD - Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. EP - 10651 TI - Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers. VL - 66 SP - 10647 KW - breast KW - cancer KW - caveolin-1 KW - cyclin KW - stem_cell KW - tumor AU - Sotgia, F AU - Rui, H AU - Bonuccelli, G AU - Mercier, I AU - Pestell, RG AU - Lisanti, MP PY - 2006/11/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-06-2805 ER -