Suppression of staurosporine-mediated apoptosis in Hs578T breast cells through inhibition of neutral-sphingomyelinase by caveolin-1.
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.
Wu
Ping
P
Center for Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Qi
Baoju
B
Zhu
Hua
H
Zheng
Yamin
Y
Li
Fei
F
Chen
Jianwen
J
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000494:pharmacology*; D002518:Ceramides / Q000378:metabolism; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D051242:Caveolin 1; D002518:Ceramides; D051057:Proto-Oncogene Proteins c-akt; C491484:SMPD3 protein, human; D013108:Sphingomyelin Phosphodiesterase; D019311:Staurosporine