Caveolin 1 is a 21 24 kDa major integral membrane pro tein on caveolae, an invaginated structure on cellular membranes enriched with high numbers of cholesterol, glycosphingolipid selleckchem Volasertib and signaling molecules. Caveolin 1 has been suggested to negatively regulate many different signaling molecules located on caveolae via mutual inter actions that compartmentalize the signaling molecules and suppress cell growth. Caveolin 1 is functionally involved in endocytosis, transcytosis, cholesterol trans port, homeostasis, negative regulation of Ras, NO, and G protein coupled receptors, and growth factor mediated protein kinase signaling cascades. There is growing evidence that loss of caveolin 1 e pres sion is associated with tumorigenesis.

Down reg ulation or absence of caveolin 1 e pression has been found in many human cancers, including primary breast, prostate, and colon cancers. Furthermore, caveo lin 1 null mice are more susceptible to carcinogen induced tumorigenesis, suggesting that caveolin 1 may be a tumor suppressor. There is accumulating e perimental evidence in vivo and in vitro that caveolin 1 e pression sensitizes cells to apop totic stimulation. Elevated e pression of endogenous caveolin 1 is associated with induction of apoptosis in mouse peritoneal macrophages. Ectopic e pression of caveolin 1 in NIH3T3 cells and T24 human bladder car cinoma cells sensitizes cells to staurosporine induced apoptosis. These data demonstrate that an up regula tion of caveolin 1 may be involved in promoting cell apoptosis.

In the present study, we investigated the effects of caveo lin 1 on pituitary adenoma shrinkage in response to bro mocriptine treatment at clinically relevant concentrations in GH3 cells. Here we show that caveolin 1 in GH3 cells was up regulated after bromocriptine treatment. Our data show that increased caveolin 1 e pression sensitizes pitu itary adenoma GH3 cells to apoptosis induced by bro mocriptine treatment and clarifies the molecular mechanism of bromocriptine therapy of pituitary ade noma. Results Ectopic e pression of recombinant caveolin 1 in GH3 cells results in apoptotic phenotypes Caveolin 1 is associated with apoptosis and has been detected in GH3 cells. As bromocriptine stimulates GH3 cell shrinkage and apoptosis, we hypothesized that bromocriptine treatment would induce GH3 cell apopto sis via caveolin 1.

Semi quantitative RT PCR was used to detect the amount of caveolin 1 mRNA in rat GH3 cells before and after bromocriptine administration at different dosages according previous report. Caveolin 1 mRNA was elevated after 24 hours of bromocriptine treatment in a dose dependent manner. To e plore the function of caveolin 1 in GH3 cells, Batimastat a pcDNA4 Caveolin 1 plasmid containing Myc tagged mouse caveolin 1 under the control of the CMV promoter was constructed and successfully transfected into GH3 cells.