title: Effects of MAP kinase inhibitors on epidermal growth factor-induced neoplastic transformation of human keratinocytes.
abstract: 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 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.
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
authors.forename: Hideya
authors.initials: H
authors.lastname: Mizuno
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases