Suzuki T, Suzuki Y, Hanada K, Hashimoto A, Redpath J L, Stanbridge E J, Nishijima M, Kitagawa T
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan.
J Biochem. 1998 Aug;124(2):383-8. doi: 10.1093/oxfordjournals.jbchem.a022123.
Studies on human cell hybrids of a cervical carcinoma cell line, HeLa, and normal fibroblasts have indicated that the tumorigenicity of these cells is under the control of a putative tumor suppressor on chromosome 11, although the nature of this suppressor remains unknown. We examined the expression of caveolin-1, a protein component of caveolae of the plasma membrane in these cell hybrids. The non-tumorigenic cell hybrid, CGL1, and normal fibroblast WI38 cells expressed 21-24 kDa caveolin-1, whereas in tumorigenic hybrid CGL4 as well as in the parental HeLa cells, the level of caveolin-1 was markedly reduced. Caveolin-1 expression was also reduced in gamma-ray-induced tumorigenic clones (GIMs) isolated from CGL1 cells, whereas non-tumorigenic irradiated cells expressed the same level of caveolin-1 as CGL1 cells. In accordance with 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 transfection of a human caveolin-1 cDNA. These results suggest that reduction of caveolin-1 expression is necessary but not sufficient for emergence of the tumorigenic phenotypes of HeLa cell hybrids. Possible roles of the putative tumor suppressor in the control of gene expression are also discussed.
对子宫颈癌细胞系HeLa与正常成纤维细胞的人细胞杂交体的研究表明，这些细胞的致瘤性受11号染色体上一种假定的肿瘤抑制因子的控制，尽管这种抑制因子的性质尚不清楚。我们检测了这些细胞杂交体中质膜小窝的一种蛋白质成分小窝蛋白-1的表达。非致瘤性细胞杂交体CGL1和正常成纤维细胞WI38表达21 - 24 kDa的小窝蛋白-1，而在致瘤性杂交体CGL4以及亲代HeLa细胞中，小窝蛋白-1的水平明显降低。从小窝蛋白-1细胞分离出的γ射线诱导的致瘤性克隆（GIMs）中，小窝蛋白-1的表达也降低，而非致瘤性照射细胞表达的小窝蛋白-1水平与CGL1细胞相同。与这些变化一致，致瘤性CGL4细胞和GIMs中小窝蛋白-1 mRNA的细胞水平降低，而小窝蛋白-1基因没有任何可检测到的变化。然而，当通过转染人小窝蛋白-1 cDNA使小窝蛋白-1稳定过表达时，CGL4细胞的体内肿瘤生长并未改变。这些结果表明，小窝蛋白-1表达的降低对于HeLa细胞杂交体致瘤性表型的出现是必要的，但不是充分的。还讨论了假定的肿瘤抑制因子在基因表达控制中的可能作用。
