PMID: 11933076Apr 5, 2002Paper

Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells

Molecular Carcinogenesis
Huihong YouK Kline

Abstract

RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) induces differentiation of human breast cancer cells. Previous studies ruled out transforming growth factor-beta and c-jun N-terminal kinase involvement in VES-induced differentiation but implicated extracellular signal-regulated kinases (ERKs). Here we show that dominant-negative mutants of either mitogen-activated protein kinase kinase (MEK) 1 or ERK1 blocked VES-induced differentiation of MDA-MB-435 cells, as measured by induction of cytokeratin 18 and p21 (Waf1/Cip1) proteins. Blockage of c-jun protein expression using c-jun antisense oligonucleotides or expression of an inducible dominant-negative c-jun mutant protein inhibited VES-induced differentiation. Elevated expression of wild-type c-jun alone was sufficient to induce cellular differentiation. A role for p21 (Waf1/Cip1) is implicated, in that p21 antisense oligomers blocked VES-induced differentiation. In summary, MEK1, ERK1, the transcription factor c-jun, and the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1) play a part in VES-induced differentiation of human MDA-MB-435 breast cancer cells.

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Citations

Jul 19, 2008·Breast Cancer Research and Treatment·Thangaiyan Rabi, Anupam Bishayee
Aug 16, 2011·Genes & Nutrition·Dorrelyn PatacsilDeepak Kumar
Sep 30, 2016·Biochemistry. Biokhimii︠a︡·M A Savitskaya, G E Onischenko
Jul 14, 2007·Vitamins and Hormones·Marco Tomasetti, Jiri Neuzil
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Young-Hwa KangSoo-Jeong Lim
Sep 15, 2010·Free Radical Research·Agnieszka AugustyniakNeven Zarković
Sep 25, 2004·Experimental Biology and Medicine·Karla A LawsonKimberly Kline
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jing NiShuyuan Yeh
Mar 1, 2006·Molecular Cancer Therapeutics·Sreenivasa DonapatyMokenge P Malafa
Dec 1, 2004·The Journal of Nutrition·Kimberly KlineBob G Sanders

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