Effects of increased expression of protein kinase C on radiation-induced cell transformation

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Abstract
The in vitro oncogenic transformation of C3H 10T1/2 cells by ionizing radiation is known to be enhanced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). It is also known that the activation of protein kinase C (PKC) by TPA is an important step in its tumor-promoting effect. In the present study, we examined the effects of overexpression of a specific isoform of PKC, PKCβ1 on 7-ray-induced transformation of 10T1/2 cells. In addition, the effects of overexpression of PKCβ1 on the malignant phenotype of a previously transformed 10T1/2 cell line were also evaluated. Derivatives of 10T1/2 cells that stably overexpress PKCβ1 were obtained by transduction with the retroviral expression vector pMV7 carrying the rat PKCβ1 cDNA sequence. We found that the parental 10T1/2 cells and a control cell line 10T1/2 MV7, which carried only the pMV7 vector without the cDNA insert, expressed dose-dependent transformation frequencies when exposed to 7-rays. On the other hand, concurrently treated PKC-overexpressing cells that had an 11-fold increase in enzyme activity (PKC-4 cells) failed to yield any morphologically identifiable foci. Cell lines that expressed lower levels of PKCβ1 were partially resistant to transformation by γ-rays. Clonogenic survival data indicated that this observation was not due to radioresistance per se. Thus, overexpression of PKCβ1 did not appear to function as an endogenous substitute for TPA in promoting radiation-induced transformation. Furthermore, overexpression of PKC did not reverse the transformation phenotypes in tumorigenic 10T1/2 cells once it was established. These findings are discussed with respect to the specific roles of individual isoforms of PKC in growth control.

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