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Decreased levels of protein kinase C enzyme activity and protein kinase C mRNA in primary colon tumors. 1993

M F Levy, and J Pocsidio, and J G Guillem, and K Forde, and P LoGerfo, and I B Weinstein
Columbia University, Comprehensive Cancer Center, College of Physicians and Surgeons, New York, New York 10032.

OBJECTIVE We have previously reported decreased protein kinase C (PKC) enzyme activity in primary human colorectal carcinomas. The purpose of this study was to extend these findings to a larger number of cases and to also examine the levels of expression of mRNAs that encode specific isoforms of PKC in these tumors. METHODS Colorectal carcinomas and paired grossly normal adjacent mucosal samples were collected from 39 patients. Complete histopathologic analyses were performed on all samples. PKC enzyme activity in both the cytosolic and particulate fractions was quantitated by measuring the amount of 32P incorporated into histone Type III-S. Northern blot nucleic acid hybridization was performed using polyA+ RNA extracted from both the tumor and normal tissue samples and 32P-labeled probes for specific isoforms of PKC. The paired sample t-test was used to determine the statistical significance of tumor to normal ratios of both enzyme activity and mRNA levels. RESULTS The mean value for cellular PKC enzyme activity in the colon tumors from 39 patients was about 60 percent of that found in the paired adjacent grossly normal mucosa samples (P < 0.001). The subcellular distribution of PKC activity was similar in normal and tumor samples (about 70 percent in the particulate fraction). The abundance of PKC alpha mRNAs varied considerably among 28 tumor/normal pairs, with a mean tumor to normal (T:N) ratio of 1.0 +/- 0.6 for the 9.9-kb mRNA band and 1.4 +/- 0.7 for the 3.5-kb band. The abundance of PKC beta mRNAs was decreased in 30 of 39 tumors, with a mean T:N ratio of 0.6 +/- 0.4 for both the 9.4- and 3.5-kb bands for all 39 samples (P < 0.001). None of the parameters measured correlated with Dukes stage or the grade of the tumor. CONCLUSIONS These studies extend previous evidence that total PKC enzyme activity is frequently decreased in primary human colon tumors. Our finding that this is often associated with decreased levels of PKC beta mRNA suggest that this is not simply due to post-translational down-regulation of this enzyme system. Further studies are required to determine whether these changes in PKC alpha and PKC beta mRNAs are due to altered de novo transcription or mRNA stability. It will also be of interest to examine the expression of other isoforms of PKC in colon tumors.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009693 Nucleic Acid Hybridization Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503) Genomic Hybridization,Acid Hybridization, Nucleic,Acid Hybridizations, Nucleic,Genomic Hybridizations,Hybridization, Genomic,Hybridization, Nucleic Acid,Hybridizations, Genomic,Hybridizations, Nucleic Acid,Nucleic Acid Hybridizations
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old

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