Expression of multiple isoforms of protein kinase C in normal human colon mucosa and colon tumors and decreased levels of protein kinase C β and η mRNAs in the tumors

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Abstract
Previous studies have suggested that protein kinase C (PKC) may play an important role in colon carcinogenesis and that human colon tumors have less total PKC enzyme activity than normal tissue. Because PKC is a multigene family that enocodes for at least 11 distinct isofroms, in the study reported here we analyzed the expression of six of these isoforms at the mRNA level by northern blot hybridization in 22 pairs of primary colon tumors (of various stages), and adjacent normal mucosa samples. We found that the normal mucosa samples expressed the mRNA of the following isoforms of PKC, in decreasing order of abundance: PKCδ>PKC>PKCα>PKCβ>PKCϵ. There was no consistent difference in the levels of PKCα, PKCδ, and PKCη. mRNAs between the normal mucosa and the tumor samples. PKCγ was expressed at a very low level in two of the colon tumors but could not be detected in the remaining tumors of any of the normal mucosa samples. The levels of both PKCβ and PKCη mRNAs were singificantly lower in the tumor samples than in the normal mucosa samples, and this was true of adenomas as well as Dukes' stage A, B, and Cadenocarcinomas. Furthermore, the devrease in PKCη mRNA appeared to be greater in the more poorly differentiated carcinomas. This finding in of interest becouse PKCη is normally expresed in the more differentiated cells of epithelial tissues. The devreased levels of both PKCβ and PKCη mRNAs ocurred early in the multistage process of colon carcinogenesis, as it was also seen in adenomas. The functional significane of these changes remains to be determined.