Caveolae/Caveolin-1 Are Important Modulators of Store-Operated Calcium Entry in Hs578/T Breast Cancer Cells

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Caveolin-1 is a principal component of caveolae, invaginations of the plasma membrane that are enriched in cholesterol and sphingolipids. The expression of caveolin-1 has been shown to be tightly correlated to the progression of breast cancer tumors. However, the consequences of altered caveolin-1 expression during tumor progression still remain unclear. Modification of caveolin-1 expression modulates store-operated Ca2+ entry (SOCE) in various cell types. SOCE is a ubiquitous Ca2+ entry pathway that previous studies have linked to apoptosis and tumor progression in prostate cancer cells. In this study, we tested the effect of altering caveolin-1 expression on SOCE in Hs578/T breast cancer cells. Through overexpression of caveolin-1 and small hairpin RNA (shRNA) knockdown, we generated four stable cell lines that have 3 different caveolin-1 protein levels. Cav-1 overexpression could increase SOCE activity, while knockdown of caveolin-1 significantly reduced SOCE activity. These functional consequences were correlated with changes in caveolae number in Hs578/T cells. Our results suggest alteration of SOCE by caveolin-1 expression changes could be one of the mechanisms contributing to the progression of breast cancer.
社団法人日本薬理学会の論文
2008-02-20