Effects of MAP kinase inhibitors on epidermal growth factor-induced neoplastic transformation of human keratinocytes

被引：17
作者：
Mizuno, H [1 ]
Cho, YY [1 ]
Ma, WY [1 ]
Bode, AM [1 ]
Dong, ZG [1 ]
机构：
[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
来源：
MOLECULAR CARCINOGENESIS | 2006年 / 45卷 / 01期
关键词：
EGF; cell transformation; human keratinocyte; MAP kinase;
D O I：
10.1002/mc.20160
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We previously reported data regarding the mechanism of neoplastic transformation in JB6 CI41 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 alpha and beta (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. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码：1 / 9
页数：9
相关论文
共 76 条
[51]  
Lage A, 2003, ANN MED, V35, P327, DOI 10.1080/07853890310010889
[52]   P53 MUTATIONS IN HUMAN IMMORTALIZED EPITHELIAL-CELL LINES [J].
LEHMAN, TA ;
MODALI, R ;
BOUKAMP, P ;
STANEK, J ;
BENNETT, WP ;
WELSH, JA ;
METCALF, RA ;
STAMPFER, MR ;
FUSENIG, N ;
ROGAN, EM ;
HARRIS, CC .
CARCINOGENESIS, 1993, 14 (05) :833-839
[53]  
Liu GM, 2001, CANCER RES, V61, P5749
[54]   TRANSFORMATION SUPPRESSOR ACTIVITY OF A JUN TRANSCRIPTION FACTOR LACKING ITS ACTIVATION DOMAIN [J].
LLOYD, A ;
YANCHEVA, N ;
WASYLYK, B .
NATURE, 1991, 352 (6336) :632-638
[55]   In situ visualization of intratumor growth factor signaling -: Immunohistochemical localization of activated ERK/MAP kinase in glial neoplasms [J].
Mandell, JW ;
Hussaini, IM ;
Zecevic, M ;
Weber, MJ ;
VandenBerg, SR .
AMERICAN JOURNAL OF PATHOLOGY, 1998, 153 (05) :1411-1423
[56]   TRANSFORMATION OF MAMMALIAN-CELLS BY CONSTITUTIVELY ACTIVE MAP KINASE KINASE [J].
MANSOUR, SJ ;
MATTEN, WT ;
HERMANN, AS ;
CANDIA, JM ;
RONG, S ;
FUKASAWA, K ;
VANDEWOUDE, GF ;
AHN, NG .
SCIENCE, 1994, 265 (5174) :966-970
[57]   Multiple positive and negative regulators of signaling by the EGF-receptor [J].
Moghal, N ;
Sternberg, PW .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (02) :190-196
[58]   Immortalization of human cells and las mechanisms [J].
Namba, M ;
Mihara, K ;
Fushimi, K .
CRITICAL REVIEWS IN ONCOGENESIS, 1996, 7 (1-2) :19-31
[59]   Involvement of the Akt/mTOR pathway on EGF-induced cell transformation [J].
Nomura, M ;
He, ZW ;
Koyama, I ;
Ma, WY ;
Miyamoto, K ;
Dong, ZG .
MOLECULAR CARCINOGENESIS, 2003, 38 (01) :25-32
[60]   Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells [J].
Oldham, SM ;
Clark, GJ ;
Gangarosa, LM ;
Coffey, RJ ;
Der, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (14) :6924-6928
12345678