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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
Author(s) -
Lin ShyrYi,
Liang YuChih,
Ho YuanSoon,
Tsai ShuHuei,
Pan Shiann,
Lee WenSen
Publication year - 2002
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10070
Subject(s) - protein kinase c , biology , mitogen activated protein kinase kinase , map kinase kinase kinase , cyclin dependent kinase 2 , map2k7 , 12 o tetradecanoylphorbol 13 acetate , kinase , protein kinase a , mapk/erk pathway , microbiology and biotechnology , c raf , staurosporine , ask1 , cyclin dependent kinase 9 , downregulation and upregulation , signal transduction , mitogen activated protein kinase , mapk14 , biochemistry , phorbol ester , gene
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, PKCγ 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. © 2002 Wiley‐Liss, Inc.