Studies on protein kinase C and colon carcinogenesis.
To further understand the molecular mechanisms of bile acid-mediated colon tumor promotion, we have examined the possible role of protein kinase C (PKC) in this process. Protein kinase C has been implicated in tumor promotion because it is the receptor for the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and mediates the action of this compound as well as that of other tumor promoters and growth factors. Our studies show that, in a manner analogous to 12-0-tetradecanoyl-phorbol-13-acetate, deoxycholic acid (DOA) can induce a time-dependent cellular redistribution of PKC as well as a concentration-dependent overexpression of the ornithine decarboxylase gene. These results taken together with our previous findings demonstrating decreased levels of PKC in human colon carcinomas compared with adjacent normal mucosa provide evidence that PKC has a role in colon carcinogenesis.
Department of Surgery, Columbia-Presbyterian Medical Center, Columbia University, New York, NY 10032.
J G
JG
Guillem
C A
CA
O'Brian
C J
CJ
Fitzer
M D
MD
Johnson
K A
KA
Forde
P
P
LoGerfo
I B
IB
Weinstein
D000818:Animals; D002273:Carcinogens; D002462:Cell Membrane / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000209:etiology*; D003600:Cytosol / Q000201:enzymology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005796:Genes / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D012334:RNA, Neoplasm; D003840:Deoxycholic Acid; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase