Large increases in caveolin 1 e pression have also been observed in apop totic agent treated mouse peritoneal macrophages. In addition, retrovirus insertion mediated random muta genesis applied to L292 cells revealed caveolin 1 is neces sary for apoptosis induced by TNF . These reports highlight a growing body of evidence indicating that up regulated e pression of caveolin 1 is associated with cell apoptosis. This study has now shown, for the first time, that caveolin 1 itself induces apoptosis of rat anterior pituitary epithelial cells of the GH3 cell line. We have shown that caveolin 1 mRNA e pression was fur ther enhanced in GH3 cells after 24 hours of bromocrip tine stimulation. It is known that with bromocriptine stimulation of GH3 cells leads to accumulation of wild type p53.

There are two consensus half sites in the caveolin 1 promoter that are predicted to be wild type p53 binding sites. Previ ous e periments have also shown that transfection of wild type p53 into human skin fibroblasts is accompanied by a si fold increase in caveolin 1 promoter transcription activity. Therefore, and supported by evidence from this study, we speculate that bromocriptine enhances caveolin 1 e pression via an increase in wild type p53 e pression in GH3 cells. Caspases play critical roles in the initiation and e ecution of the apoptotic process. We found that, at least in part, caspase 8 might be required for caveolin 1 induction of GH3 cell apoptosis. In contrast, up regulation of cave olin 1 sensitizes NIH3T3 fibroblasts and T24 bladder car cinoma epithelial cells to apoptotic stimuli via increased activation of caspase 3.

Caveolin 1 up regulation is also associated with simvastatin induced apoptosis of thi oglycollate elicited mouse peritoneal macrophages. this effect was independent of caspase activity, because the general caspase inhibitor Z VAD Fmk failed to block cell death. Together these results indicate caveolin 1 mediates cellular apoptosis through variant signaling pathways in different cell types. Treatment of lymphocytes and NIH3T3 cells with H2O2 or UV light induces phosphorylation of caveolin 1 Tyr14. In addition, caveolin 1 phosphorylated at Tyr14 specifically co localizes with pa illin at focal adhesion Dacomitinib comple es after epidermal growth factor, insulin or H2O2 treatment, suggesting phosphorylation of caveolin 1 is associated with cellular morphological changes and shrinkage when cells adapt to e ternal cellular stresses. In addition, etoposide, a therapeutic agent for leukemia, in inducing tumor cell apoptosis, increases phosphorylation of caveolin 1 Tyr14 in HL 60 cells.