Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RRR-alpha-Tocopheryl succinate (vitamin E succinate, VES) is a potent antitumor agent, inducing DNA synthesis arrest, differentiation, and apoptosis. Because little is known about VES-induced differentiation, studies reported here characterize VES effects on the differentiation status of human breast cancer cell lines and investigate possible molecular mechanisms involved. VES-induced differentiation of human MCF-7 and MDA-MB-435 breast cancer cells was characterized by morphological changes, induction of lipid droplets, induction of beta-casein mRNA expression, and down-regulation of Her2/neu protein. In contrast, VES treatment of normal human mammary epithelial cells, MCF-10A cells, and T-47D cells did not induce differentiation. Studies addressing mechanisms showed that neither antibody neutralization of the transforming growth factor-beta signaling pathway nor expression of a dominant-negative mutant of c-Jun N-terminal kinase blocked the ability of VES to induce differentiation; however, treatment of cells with PD 98059, a chemical inhibitor of mitogen-activated protein kinase kinase (MEK1/2), blocked the ability of VES to induce differentiation.
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PMID:RRR-alpha-tocopheryl succinate induces MDA-MB-435 and MCF-7 human breast cancer cells to undergo differentiation. 1157 Dec 30

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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PMID:Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells. 1193 76