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 encodes for at least 11 distinct
isoforms, 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 mRNAs of the following
isoforms of PKC, in decreasing order of abundance: PKC delta >
PKC eta > PKC alpha >
PKC beta >
PKC epsilon. There was no consistent difference in the levels of PKC alpha, PKC delta, and
PKC epsilon mRNAs between the normal mucosa and the
tumor samples.
PKC gamma was expressed at a very low level in two of the colon
tumors but could not be detected in the remaining
tumors or any of the normal mucosa samples. The levels of both
PKC beta and
PKC eta mRNAs were significantly 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 C
adenocarcinomas. Furthermore, the decrease in
PKC eta mRNA appeared to be greater in the more poorly differentiated
carcinomas. This finding is of interest because
PKC eta is normally expressed in the more differentiated cells of epithelial tissues. The decreased levels of both
PKC beta and
PKC eta mRNAs occurred early in the multistage process of colon
carcinogenesis, as it was also seen in
adenomas. The functional significance of these changes remains to be determined.