Yehiely F, Oren M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Cell Growth Differ. 1992 Nov;3(11):803-9.
In cells transformed by mutant mouse p53 plus ras, the former protein is found to be complexed with the heat-shock protein cognate hsc70. To determine whether hsc70 can directly affect neoplastic transformation, nonestablished rat embryo fibroblasts (REF) were transfected with rat genomic hsc70 DNA in conjunction with various oncogenes. We report here that the hsc70 gene could efficiently suppress focus induction by mutant p53 plus ras, as well as by myc plus ras. No inhibitory effect of hsc70 was detectable in assays monitoring the ability of REF to be immortalized by mutant p53, arguing against a nonspecific deleterious effect of the hsc70 genomic clone on REF survival and proliferation. Lines generated in the presence of the hsc70 plasmid produced augmented levels of hsc70. Plasmids encoding only short NH2-terminal fragments of hsc70 could also, in some cases, partially reduce oncogene-mediated focus formation. However, a maximal inhibitory effect required the production of a functional hsc70 protein. The data presented here raise the possibility that hsc70 may be directly involved in the modulation of oncogene-mediated transformation.
在由突变型小鼠p53与ras基因共同转化的细胞中，发现前一种蛋白与热休克蛋白同源物hsc70形成复合物。为了确定hsc70是否能直接影响肿瘤转化，将大鼠基因组hsc70 DNA与各种癌基因一起转染未建立的大鼠胚胎成纤维细胞（REF）。我们在此报告，hsc70基因能够有效抑制由突变型p53与ras基因共同诱导的集落形成，以及由myc与ras基因共同诱导的集落形成。在监测REF被突变型p53永生化能力的实验中，未检测到hsc70有抑制作用，这表明hsc70基因组克隆对REF的存活和增殖不存在非特异性有害影响。在hsc70质粒存在的情况下产生的细胞系中，hsc70的水平有所提高。在某些情况下，仅编码hsc70短NH2末端片段的质粒也能部分减少癌基因介导的集落形成。然而，最大抑制作用需要产生功能性的hsc70蛋白。本文提供的数据表明，hsc70可能直接参与癌基因介导的转化调控。
