Overexpression of protein kinase C beta 1 in the SW480 colon cancer cell line causes growth suppression.
Using a retroviral vector system we have established derivatives of the E8 subclone of the human colon cancer cell line SW480 that stably overproduce a full-length rat cDNA encoding the beta 1 isoform of protein kinase C (PKC beta 1). In contrast to vectrol control cells, when treated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the overexpressing cell lines displayed a striking increase in doubling time, and a decrease in saturation density. Western blot analysis indicated that treatment with TPA was also associated with translocation and partial downregulation of the exogenous PKC beta 1 in the over-expressor cell lines. These results extend previous evidence that PKC beta 1 can inhibit the growth of the HT29 human colon cancer cell line. The HT29 cells have a normal c-k-ras oncogene but the SW480 cells used in the present study have an activating mutation in this oncogene. Thus PKC beta 1 can function as a suppressor in both types of colon cancer cells.
Goldstein
D R
DR
Columbia-Presbyterian Cancer Center, College of Physicians and Surgeons, Columbia University, New York 10032, USA.
Cacace
A M
AM
Weinstein
I B
IB
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D011994:Recombinant Proteins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate