Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast cancer cells.
Estrogen, which has been strongly implicated in breast cancer, suppresses apoptosis in estrogen receptor (ER) positive MCF-7 breast cancer cells. Phospholipase D (PLD), which is commonly elevated in ER negative breast cancer cells, also suppresses apoptosis. Survival signals generated by both estrogen and PLD are dependent upon elevated Myc expression. We report here that estrogen- and PLD-induced increases in Myc expression are due to reduced turnover of Myc protein. Estrogen and PLD suppressed phosphorylation of Myc at Thr58--a site that targets Myc for degradation by the proteasome. The data provide a mechanism for elevated Myc expression in hormone-dependent and hormone-independent breast cancer.
Rodrik
Vanessa
V
Department of Biological Sciences, Hunter College of The City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Gomes
Evan
E
Hui
Li
L
Rockwell
Patricia
P
Foster
David A
DA
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
D004967:Estrogens; D016271:Proto-Oncogene Proteins c-myc; D010769:Phosphothreonine; D010768:Phosphoserine; D004958:Estradiol; D038362:Glycogen Synthase Kinase 3; D010739:Phospholipase D