PMID: 9531502Jun 11, 1998Paper

Involvement of the Ras/extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin

The Biochemical Journal
W Lee-KwonM Bernier

Abstract

Expression of DNA repair enzymes, which includes ERCC-1, might be under the control of hormonal and growth factor stimulation. In the present study it was observed that insulin increased ERCC-1 mRNA levels both in Chinese hamster ovary cells overexpressing human insulin receptors (HIRc cells) and in fully differentiated 3T3-L1 adipocytes. To investigate the mechanisms underlying the increase in ERCC-1 gene expression in HIRc cells, we used a variety of pharmacological tools known to inhibit distinct signalling pathways. None of these inhibitors affected the amount of ERCC-1 mRNA in unstimulated cells. The pretreatment of cells with two chemically unrelated phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, failed to block the doubling of ERCC-1 mRNA content by insulin. Similarly, inhibition of pp70 S6 kinase by rapamycin had no apparent effects on this insulin response. In contrast, altering the p21(ras)-dependent pathway with either manumycin, an inhibitor of Ras farnesylation, or PD98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase, suppressed the induction of ERCC-1 mRNA by insulin (P<0.001). Furthermore inhibition of RNA and protein synthes...Continue Reading

Citations

Jul 15, 2009·Nature Reviews. Clinical Oncology·Yohann LoriotJean-Charles Soria
Mar 6, 2002·The Journal of Biological Chemistry·Lisa Héron-Milhavet, Derek LeRoith
Oct 7, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ju-Pi LiJia-Ling Yang
Jan 14, 2018·Molecular Cancer Research : MCR·Rei MizunoAnil K Rustgi
May 9, 2000·Biochemical and Biophysical Research Communications·I Shin, J S Han
Oct 2, 2001·Pharmacology & Therapeutics·M LeszczynieckaP B Fisher
Feb 22, 2005·Biochemical and Biophysical Research Communications·Shinhae KangDeokbae Park

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