| Over the last few decades there have been outstanding advances in breast cancer management leading to earlier detection of disease and the development of more effective treatments resulting in significant declines in breast cancer deaths and improved outcomes for women living with the disease. Breast cancer is a multifaced disease comprised of distinct biological subtypes with different prognostic and therapeutic implications molecular features.Caveolin-1(Cav-1) is the major protein component of caveolae, specialized lipid rafts that are recognized in electron micrographs as 50-100nm invaginations of plasma membrane. Proveriously, we established a Cav-1 haploinsufficiency cell line, we found that Cav-1 down-regulation could activate the express of ERα, lead to partial transformation of human breast epithelial cells. Our newly established cell mode-- MCF10ACE expressed a low level of Caveolin-1 and a high level of ERα36. The result shows Caveolin-1 down-regulation strengthens the interaction of ERα-Caveolin-1. Furthermore, Cav-1 gene silencing activates the PI3K/AKT signaling pathway witch dependent on ERα36 was detected. Further investigating ERα36 mediated the cross-talk between PI3K/AKT and MEK/ERK pathways to promote cell growth. Therefore, Caveolin-1 maybe works as a negative regulator of the survival, growth and progression pathway to mediate mammary epithelia cell transformation by ERα36. ERα36 plays an important role in mammary tumorigensis in vitro and may be a potential target for mediating the membrane initiated estrogen-signaling pathway.
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