Deficiency of tyrosine phosphorylation in a Balb/c 3T3 cell variant hypersensitive to phorbol ester-induced cell transformation.
To identify the cellular factors which are involved in tumor promotion, we isolated and cloned a Balb/c 3T3 variant (designated Balb/c 3T3 TR4) showing hypersensitivity to phorbol ester-induced neoplastic cell transformation; variant cells were 50- to 100-fold more sensitive to phorbol ester induced cell transformation than the parent Balb/c 3T3 A31-1-1 cells. By using an anti-phosphotyrosine antibody, the variant TR4 cells were found to be deficient in the phorbol ester-induced tyrosine-phosphorylation of a cellular protein with a mol. wt of 66 kDa. The phosphorylation of this protein was rapidly induced by phorbol ester tumor promoters on tyrosine residues in the parent 1-1 cells. Biological and biochemical analyses using fusion cells revealed a good correlation between the deficiency in the tyrosine phosphorylation of this protein and their sensitivity to phorbol ester-induced cell transformation, suggesting that the deficiency in phorbol ester-induced tyrosine phosphorylation of the 66 kDa protein may be involved in the determination of the sensitivity of TR4 variant cells to phorbol ester-mediated neoplastic cell transformation. In addition, our observations suggest the possible involvement of the modulation of tyrosine phosphorylation of cellular proteins in the process of phorbol ester-mediated tumor promotion.
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
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D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D008748:Methylcholanthrene; D013755:Tetradecanoylphorbol Acetate