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Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells.
Mol Carcinog. 2002 Apr; 33(4):228-36.MC

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.

Authors+Show Affiliations

Department of Molecular Genetics and Microbiology/C0900 School of Biological Sciences, The University of Texas at Austin, 78712-1097, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11933076

Citation

You, Huihong, et al. "Role of Extracellular Signal-regulated Kinase Pathway in RRR-alpha-tocopheryl Succinate-induced Differentiation of Human MDA-MB-435 Breast Cancer Cells." Molecular Carcinogenesis, vol. 33, no. 4, 2002, pp. 228-36.
You H, Yu W, Munoz-Medellin D, et al. Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells. Mol Carcinog. 2002;33(4):228-36.
You, H., Yu, W., Munoz-Medellin, D., Brown, P. H., Sanders, B. G., & Kline, K. (2002). Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells. Molecular Carcinogenesis, 33(4), 228-36.
You H, et al. Role of Extracellular Signal-regulated Kinase Pathway in RRR-alpha-tocopheryl Succinate-induced Differentiation of Human MDA-MB-435 Breast Cancer Cells. Mol Carcinog. 2002;33(4):228-36. PubMed PMID: 11933076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of extracellular signal-regulated kinase pathway in RRR-alpha-tocopheryl succinate-induced differentiation of human MDA-MB-435 breast cancer cells. AU - You,Huihong, AU - Yu,Weiping, AU - Munoz-Medellin,Debbie, AU - Brown,Powel H, AU - Sanders,Bob G, AU - Kline,Kimberly, PY - 2002/4/5/pubmed PY - 2002/5/10/medline PY - 2002/4/5/entrez SP - 228 EP - 36 JF - Molecular carcinogenesis JO - Mol Carcinog VL - 33 IS - 4 N2 - 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. SN - 0899-1987 UR - https://www.unboundmedicine.com/medline/citation/11933076/Role_of_extracellular_signal_regulated_kinase_pathway_in_RRR_alpha_tocopheryl_succinate_induced_differentiation_of_human_MDA_MB_435_breast_cancer_cells_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0899-1987&date=2002&volume=33&issue=4&spage=228 DB - PRIME DP - Unbound Medicine ER -