Effect of Caveolin-1 upon Stat3-ptyr705 levels in breast and lung carcinoma cells.

We recently demonstrated that Cav1 is a negative regulator of Stat3 activity in mouse fibroblasts and human lung carcinoma SHP77 cells. We now examined whether the cellular context may affect their levels and relationship between them, by assessing Cav1 and Stat3-ptyr705 levels in different lines. In MDA-MB-231, A549 and HaCat cells Cav1 levels were high and Stat3-ptyr705 levels were low, consistent with the notion of a negative effect of the endogenous Cav1 upon Stat3-ptyr705 levels in these lines. In addition, manipulation of Cav1 levels revealed a negative effect in MCF7 and mouse fibroblast cells, while Cav1 upregulation induced apoptosis in MCF7 cells. In contrast however, line MRC9 had high Cav1 and high Stat3-ptyr705 levels, indicating that the high Cav1 is insufficient to reduce Stat3-ptyr705 levels in this line. MCF7 and LuCi6 cells had very low Cav1 and Stat3-ptyr705 levels, indicating that the low Stat3-ptyr705 can be independent from Cav1 levels altogether. Our results reveal a further level of complexity in the relationship between Cav1 and Stat3-ptyr705 than previously thought. In addition, we demonstrate that, in a feedback loop, Stat3 inhibition upregulates Cav1 in HeLa cells but not in other lines tested.