Suppressive function of RKTG on chemical carcinogen-induced skin carcinogenesis in mouse.
Raf kinase trapping to Golgi (RKTG) is a newly characterized negative regulator of the Ras-Raf-MEK-ERK signaling pathway via sequestrating Raf-1 to the Golgi apparatus. However, little is known about the physiological functions of RKTG in mitogenic pathway and carcinogenesis. Here, we describe a suppressive role of RKTG in skin carcinogenesis by analyzing chemical carcinogen-induced tumorigenesis. Epidermis hyperplasia and proliferation are increased in RKTG-deficient mice (RKTG(-/-)) after acute treatment with 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Using a two-stage DMBA/TPA carcinogenesis protocol on mouse skin, the number and size of papillomas are increased in RKTG(-/-) mice, accompanied by shortened tumor latency and enhanced keratinocyte proliferation. The regression of the carcinogen-induced tumors is also prolonged in RKTG(-/-) mice. Consistently, the levels of Raf-1 and extracellular signal-regulated kinase phosphorylation in primary keratinocytes as well as skin tumors are elevated when RKTG is disrupted. Collectively, our results indicate that RKTG has a suppressive activity in chemical carcinogen-induced mitogenesis and tumor formation in mouse skin.
Xie
Xiaoduo
X
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Yixuan
Y
Jiang
Yuhui
Y
Liu
Weizhong
W
Ma
Hong
H
Wang
Zhenzhen
Z
Chen
Yan
Y
D000818:Animals; D016588:Anticarcinogenic Agents; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002455:Cell Division; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D025521:Tumor Suppressor Proteins / Q000502:physiology
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C523677:RKTG protein, mouse; D025521:Tumor Suppressor Proteins; D001973:Bromodeoxyuridine