Expression of multiple isoforms of protein kinase C in normal human colon mucosa and colon tumors and decreased levels of protein kinase C beta and eta mRNAs in the tumors.
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.
Doi
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Columbia-Presbyterian Cancer Center, College of Physicians and Surgeons of Columbia University, New York, NY 10021.
Goldstein
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Hug
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Weinstein
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D000236:Adenoma / Q000201:enzymology; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015152:Blotting, Northern; D003106:Colon / Q000201:enzymology* / Q000502:physiology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000502:physiology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; D011493:Protein Kinase C