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Suppression of staurosporine-mediated apoptosis in Hs578T breast cells through inhibition of neutral-sphingomyelinase by caveolin-1.

Wu P, Qi B, Zhu H, Zheng Y, Li F, Chen J

Center for Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Caveolin-1, a 21-24kDa integral membrane protein, is a principal structural component of caveolae in vivo. To investigate the roles of caveolin-1, we established stable transfectants in Hs578T breast adenocarcinoma cells that had up- and down-regulated caveolin-1 expression. In the paper, we demonstrated that caveolin-1 overexpression in Hs578T cells significantly reduced staurosporine-induced apoptosis and the levels of caveolin-1 expression positively correlated with the number of colonies and colony size in soft agar. Our findings indicate for the first time in Hs578T cells that caveolin-1 might play a pivotal role in regulating apoptosis as a suppressor rather than a facilitator through inhibition of neutral-sphingomyelinase, decrease of ceramide, furthermore, activation of Akt signaling pathway.

Published 5 September 2007 in Cancer Lett, 256(1): 64-72.
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