Abstract
Constitutive activation of estrogen receptor alpha (ER-α) expression is an early event in breast cancer tumorigenesis. However, the mechanism whereby ER-α is constitutively activated during transformation of normal mammary cells has not been well established. Previously, we reported that haploinsufficiency of caveolin-1, a major structural protein that forms caveolae, resulted in anchorage-independent growth of a normal mammary epithelial cell line, MCF10A. Here, we further demonstrated that ER-α but not ER-β expression was constitutively activated in these caveolin-1 haploinsufficient cells. Transient treatment of MCF10A cells with β-methyl-cyclodextrin, a chemical that can displace caveolin-1 from the plasma membrane, also stimulated ER-α expression. We further found that the 17β-estradiol (E2) accelerated anchorage-independent growth of these cells in vitro and promoted their tumorigenesis in nude mice. These results suggest that dysregulation of caveolin-1 is one of the mechanisms by which ER-α expression is activated during initiation of breast tumorigenesis.