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Carcinogenesis Advance Access originally published online on May 29, 2008
Carcinogenesis 2008 29(6):1157-1163; doi:10.1093/carcin/bgn119
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

RKTG sequesters B-Raf to the Golgi apparatus and inhibits the proliferation and tumorigenicity of human malignant melanoma cells

Fengjuan Fan, Lin Feng, Jing He, Xiao Wang, Xiaomeng Jiang, Yixuan Zhang, Zhenzhen Wang and Yan Chen*

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China

* To whom correspondence should be addressed. Tel: +86 21 54920916; Fax: +86 21 54920291; Email: ychen3{at}sibs.ac.cn

Raf kinase trapping to Golgi (RKTG) is a newly characterized negative regulator of the Ras–Raf–mitogen-activated and extracellular signal-regulated kinase kinase (MEK)–extracellular signal-regulated kinase (ERK)-signaling pathway via sequestrating Raf-1 to the Golgi apparatus. Among Raf kinase family members, B-Raf is the most frequently mutated gene in human cancers and an activated B-Raf mutation V600E is associated with >60% of human melanomas. Here, we show that RKTG can also bind and translocate B-Raf to the Golgi apparatus. When overexpressed in A375, a human malignant melanoma cell line with B-Raf(V600E), RKTG inhibits ERK activation, cell proliferation and transformation of A375 cells. In addition, the tumorigenicity of the RKTG-expressing A375 cells is suppressed in nude mice. Consistently, cell proliferation rate was reduced in the tumor xenografts in which RKTG was overexpressed. Collectively, our results suggest that RKTG may play a suppressive role in human melanoma that harbors an oncogenic B-Raf mutation via its antagonistic action on B-Raf.

Abbreviations: DMEM, Dulbecco's modified Eagle's medium; EGF, epidermal growth factor; ERK, extracellular signal-regulated kinase; MEK, mitogen-activated and extracellular signal-regulated kinase kinase; MM, malignant melanoma; RKTG, Raf kinase trapping to Golgi

Received January 17, 2008; revised April 11, 2008; accepted May 6, 2008.


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