Mizuno Hideya, Cho Yong-Yeon, Ma Wei-Ya, Bode Ann M, Dong Zigang
Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Mol Carcinog. 2006 Jan;45(1):1-9. doi: 10.1002/mc.20160.
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.
我们之前报道了关于JB6 Cl41小鼠皮肤表皮细胞肿瘤转化机制的数据。然而，用于研究人类细胞肿瘤转化的体外实验模型可以为人类癌症发展机制提供进一步的见解。在本研究中，我们建立了一个以人角质形成细胞系HaCaT细胞为基础的肿瘤转化模型，并证明了该细胞系在研究肿瘤转化机制方面的实用性。表皮生长因子（EGF）处理在HaCaT细胞中诱导了剂量依赖性的不依赖贴壁的细胞转化。此外，丝裂原活化蛋白（MAP）激酶/ERK激酶（MEK）抑制剂PD98059或c-Jun氨基末端激酶（JNK）抑制剂SP600125可降低细胞生长、EGF诱导的DNA合成和细胞转化。与在JB6小鼠表皮细胞模型中的观察结果不同，应激激活蛋白激酶-2/p38α和β（p38）抑制剂SB203580增加了EGF诱导的HaCaT细胞转化。这些结果表明，细胞外信号调节激酶（ERK）、JNK或p38参与了EGF诱导的人类细胞肿瘤转化。
