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

✍ Scribed by Huihong You; Weiping Yu; Debbie Munoz-Medellin; Powel H. Brown; Bob G. Sanders; Kimberly Kline

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 189 KB
• Volume: 33
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.10040

✦ Synopsis

Abstract

RRR‐α‐tocopheryl succinate (vitamin E succinate, VES) induces differentiation of human breast cancer cells. Previous studies ruled out transforming growth factor‐β 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. © 2002 Wiley‐Liss, Inc.