Anti-proliferative activity of protein kinase C in apical compartments of human colonic crypts: Evidence for a less activated protein kinase C in small adenomas
✍ Scribed by Roland Assert; Ralf Kötter; Guido Bisping; Wolfgang Scheppach; Edmund Stahlnecker; Klaus M. Müller; Gerda Dusel; Helmut Schatz; Andreas Pfeiffer
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 148 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal transduction in colorectal-cell lines. Its function in human colonic mucosal proliferation is controversial. Our study investigated the role of PKC with regard to proliferation and changes of PKC iso-enzyme expression in colonic biopsies compared with small adenomas. In shortterm tissue-culture experiments of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical compartments of longitudinally sectioned crypts when PKC was activated by 200 nM of the phorbol ester TPA (n ؍ 8). Thus, PKC inhibited growth of differentiated colonocytes which may influence cell homeostasis in colonic crypts. Furthermore, we have determined the expression of PKC␣, -1, -2, -␦ and -⑀ in colonic adenomas smaller than 1 cm in diameter of 18 patients and found a significant increase of PKC␣ in the cytosolic fraction and decreased membrane levels of PKC2 in adenomas compared to normal, neighboring mucosa while protein levels of PKC1, -␦ and -⑀ were not altered. Moreover PKC␦ but not PKC␣ mRNA expression was significantly lowered in adenoma tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes in the regulation patterns of PKC isoforms suggest a decreased activation state of PKC even in small adenomas. This is compatible with an anti-proliferative function of PKC serving to protect mucosa from expanding mutated cells. Int.