Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O-tetradecanoylphorbol-13-acetate-induced upregulation of p21(Cip1) in colon cancer cells.
Protein kinase C (PKC), a family of serine-threonine kinases, has been implicated in the regulation of colon tumorigenesis. However, the specific isoform of PKC involved in this process is not clear. In the present study, we found that treatment of the cultured human colon cancer cell line COLO-205 with a PKC agonist, 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in cell-cycle arrest at the G(0)/G(1) phase, decrease in cell number, PKCgamma isoform translocation, and upregulation of p21(Cip1) protein. Pretreatment of the cells with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of p21(Cip1) protein. Based on the findings of the present study including that (a) both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) were activated in the TPA-treated COLO-205 cells, (b) pretreatment with the mitogen-activated protein kinase kinase inhibitor PD98059 but not with the p38 mitogen-activated protein kinase inhibitor SB203580 blocked the TPA-induced p21(Cip1) in COLO-205 cells, and (c) transient transfection of the COLO-205 cells with dominant negative ERK or JNK plasmid significantly suppressed the TPA-induced p21(Cip1) protein induction, we conclude that both the ERK and JNK pathways are involved in the TPA-induced upregulation of p21(Cip1) protein in the COLO-205 cells.
Lin
Shyr-Yi
SY
Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
Liang
Yu-Chih
YC
Ho
Yuan-Soon
YS
Tsai
Shu-Huei
SH
Pan
Shiann
S
Lee
Wen-Sen
WS
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007527:Isoenzymes; D011725:Pyridines; C087857:protein kinase C gamma; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one