REDUCTION OF CAVEOLIN-1 EXPRESSION IN TUMORIGENIC HUMAN CELL HYBRIDS

Studies on human cell hybrids of a cervical carcinoma cell line, HeLa, and normal fibroblasts have indicated that the tumorigenicity of thes e cells is under the control of a putative tumor suppressor on chromos ome 11, although the nature of this suppressor remains unknown. We exa mined the expression of caveolin-1, a protein component of caveolae of the plasma membrane in these cell hybrids. The non-tumorigenic cell h ybrid, CGL1, and normal fibroblast WI38 cells expressed 21-24kDa caveo lin-1, whereas in tumorigenic hybrid CGL4 as well as in the parental H eLa cells, the level of caveolin-1 was markedly reduced. Caveolin-l ex pression was also reduced in gamma-ray-induced tumorigenic clones (GIM s) isolated from CGL1 cells, whereas non-tumorigenic irradiated cells expressed the same level of caveolin-1 as CGL1 cells. In accordance wi th these changes, the cellular level of caveolin-1 mRNA was reduced in the tumorigenic CGL4 cells and GIMs without any detectable changes in the caveolin-1 gene. However, the in vivo tumor growth of CGL4 cells was not altered when caveolin-1 was stably overexpressed through the t ransfection of a human caveolin-1 cDNA, These results suggest that red uction of caveolin-1 expression is necessary but not sufficient for em ergence of the tumorigenic phenotypes of HeLa cell hybrids. Possible r oles of the putative tumor suppressor in the control of gene expressio n are also discussed.