36 Citations (Scopus)

Abstract

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 G0/G1 phase, decrease in cell number, PKCγ isoform translocation, and upregulation of p21Cip1 protein. Pretreatment of the cells with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of p21Cip1 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 p21Cip1 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 p21Cip1 protein induction, we conclude that both the ERK and JNK pathways are involved in the TPA-induced upregulation of p21Cip1 protein in the COLO-205 cells.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalMolecular Carcinogenesis
Volume35
Issue number1
DOIs
Publication statusPublished - Sep 2002

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JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Tetradecanoylphorbol Acetate
Colonic Neoplasms
Up-Regulation
Protein Kinase C
Protein Kinase Inhibitors
Protein Isoforms
Proteins
Phosphotransferases
Cell Cycle Resting Phase
Staurosporine
Protein C Inhibitor
Protein-Serine-Threonine Kinases
Mitogen-Activated Protein Kinase Kinases
G1 Phase
p38 Mitogen-Activated Protein Kinases
Cell Cycle Checkpoints
Transfection
Colon

Keywords

  • Cell cycle
  • G/G arrest
  • MAPK
  • PKCγ

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

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title = "Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O- tetradecanoylphorbol-13-acetate-induced upregulation of p21Cip1 in colon cancer cells",
abstract = "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 G0/G1 phase, decrease in cell number, PKCγ isoform translocation, and upregulation of p21Cip1 protein. Pretreatment of the cells with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of p21Cip1 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 p21Cip1 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 p21Cip1 protein induction, we conclude that both the ERK and JNK pathways are involved in the TPA-induced upregulation of p21Cip1 protein in the COLO-205 cells.",
keywords = "Cell cycle, G/G arrest, MAPK, PKCγ",
author = "Shyr-Yi Lin and Yu-Chih Liang and Yuan-Soon Ho and Shu-Huei Tsai and Shiann Pan and Wen-Sen Lee",
year = "2002",
month = "9",
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language = "English",
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T1 - Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O- tetradecanoylphorbol-13-acetate-induced upregulation of p21Cip1 in colon cancer cells

AU - Lin, Shyr-Yi

AU - Liang, Yu-Chih

AU - Ho, Yuan-Soon

AU - Tsai, Shu-Huei

AU - Pan, Shiann

AU - Lee, Wen-Sen

PY - 2002/9

Y1 - 2002/9

N2 - 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 G0/G1 phase, decrease in cell number, PKCγ isoform translocation, and upregulation of p21Cip1 protein. Pretreatment of the cells with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of p21Cip1 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 p21Cip1 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 p21Cip1 protein induction, we conclude that both the ERK and JNK pathways are involved in the TPA-induced upregulation of p21Cip1 protein in the COLO-205 cells.

AB - 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 G0/G1 phase, decrease in cell number, PKCγ isoform translocation, and upregulation of p21Cip1 protein. Pretreatment of the cells with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of p21Cip1 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 p21Cip1 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 p21Cip1 protein induction, we conclude that both the ERK and JNK pathways are involved in the TPA-induced upregulation of p21Cip1 protein in the COLO-205 cells.

KW - Cell cycle

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KW - MAPK

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