Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast cancer cells

FEBS Lett. 2006 Oct 16;580(24):5647-52. doi: 10.1016/j.febslet.2006.09.013. Epub 2006 Sep 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Estradiol / pharmacology
  • Estrogens / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Phosphorylation / drug effects
  • Phosphoserine / metabolism
  • Phosphothreonine / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism*

Substances

  • Estrogens
  • Proto-Oncogene Proteins c-myc
  • Phosphothreonine
  • Phosphoserine
  • Estradiol
  • Glycogen Synthase Kinase 3
  • Phospholipase D