TUMOR-CELL GROWTH-INHIBITION BY CAVEOLIN REEXPRESSION IN HUMAN BREAST-CANCER CELLS

Cancer development is a multistage process that results from the step- wise acquisition of somatic alterations in diverse genes, Recent studi es indicate that caveolin-1 expression correlates with the level of on cogenic transformation in NIH3T3 cells, suggesting that caveolin in ca veolae mag regulate normal cell proliferation, In order to better unde rstand potential functions of caveolin-1 in cancer development, we hav e studied expression levels of caveolin-1 in human breast cancer cells , and have found that caveolin expression is significantly reduced in human breast cancer cells compared with their normal mammary epithelia l counterparts, When the caveolin cDNA linked to the CMV promoter is t ransfected into human mammary cancer cells having no detectable endoge nous caveolin, overexpression of caveolin-1 resulted in substantial gr owth inhibition, as seen by the 50% decrease in growth rate and by sim ilar to 15-fold reduction in colony formation in soft agar, In additio n, characterization of caveolin-1 expression during cell cycle progres sion indicates that expression of alpha-caveolin-1 is regulated during cell cycle, Furthermore p53-deficient cells showed a loss in caveolin expression, In summary, the overall expression patterns, its ability to inhibit tumor growth in culture, its regulation during the cell cyc le, and the loss of expression in p53-deficient cells all are consiste nt with an important growth regulating function for caveolin-1 in norm al human mammary cells, that needs to be repressed in oncogenic transf ormation and tumor cell growth.