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Effects of MAP kinase inhibitors on epidermal growth factor‐induced neoplastic transformation of human keratinocytes
Author(s) -
Mizuno Hideya,
Cho YongYeon,
Ma WeiYa,
Bode Ann M.,
Dong Zigang
Publication year - 2005
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.20160
Subject(s) - hacat , neoplastic transformation , biology , epidermal growth factor , microbiology and biotechnology , mitogen activated protein kinase , mapk/erk pathway , kinase , protein kinase a , p38 mitogen activated protein kinases , cancer research , malignant transformation , cell culture , cancer , carcinogenesis , genetics
We previously reported data regarding the mechanism of neoplastic transformation in JB6 Cl41 mouse skin epidermal cells. However, experimental in vitro models for studying neoplastic transformation of human cells could provide further insight into the mechanisms of human cancer development. In this study, we have established a neoplastic transformation model with HaCaT cells, a human keratinocyte cell line, and showed the usefulness of this cell line for studying the mechanisms of neoplastic transformation. Epidermal growth factor (EGF) treatment induced a dose‐dependent anchorage‐independent cell transformation in HaCaT cells. Furthermore, PD98059, a mitogen‐activated protein (MAP) kinase/ERK kinase (MEK) inhibitor, or SP600125, c‐Jun N‐terminal kinase (JNK) inhibitor, decreased cell growth, EGF‐induced DNA synthesis and transformation. Unlike observations in the JB6 mouse epidermal cell model, SB203580, a stress‐activated protein kinase‐2/p38 α and β (p38) inhibitor, increased EGF‐induced transformation in HaCaT cells. These results suggest that extracellular‐signal regulated kinase (ERK), JNK, or p38 are implicated in EGF‐induced neoplastic transformation of human cells. © 2005 Wiley‐Liss, Inc.