Role of metal-responsive transcription factor-1 (MTF-1) in EGF-dependent DNA synthesis in primary hepatocytes

Journal of Cellular Biochemistry
Tomoki KimuraMasakazu Isobe

Abstract

Metal-responsive transcription factor-1 (MTF-1), which is involved in sensing heavy metal load, induces the transcription of several protective genes. The mouse Mtf-1 gene is essential, and Mtf-1(-/-) embryos die from liver degeneration. We showed that DNA synthesis induced in hepatocytes by epidermal growth factor (EGF) was delayed by inhibition of MTF-1. To inhibit MTF-1 activity, MTFDeltaC, a C-terminal deletion mutant of MTF-1, was expressed by infection with the virus Ad5MTFDeltaC. Lactate dehydrogenase (LDH) release and/or caspase-3/7 activation was not observed under our experimental conditions. The inhibitory effect of MTFDeltaC on EGF-dependent DNA synthesis in hepatocytes was not eliminated by zinc addition. EGF-dependent extracellular signal-related kinase (ERK) phosphorylation, an essential reaction for EGF-dependent DNA synthesis, was decreased in MTF-1-inhibited hepatocytes. Moreover, decrease of ERK phosphorylation was observed by using siRNA in MTF-1-downregulated hepatocytes. These results indicate that MTF-1 is particularly important for proper hepatocyte proliferation. This is the first report to suggest the function of MTF-1 in the ERK pathway.

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Sep 21, 2004·Journal of Cellular Biochemistry·Tomoki KimuraMasakazu Isobe
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Citations

Dec 7, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tomoki Kimura
Aug 2, 2012·Nutrients·Bruce J Grattan, Hedley C Freake
Dec 18, 2013·Journal of Mammary Gland Biology and Neoplasia·Nicholas H McCormickShannon L Kelleher

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