Identification of downstream targets of estrogen and c-myc in breast cancer cells

Adv Exp Med Biol. 2008;617:445-51. doi: 10.1007/978-0-387-69080-3_43.

Abstract

Estrogen (E) plays a pivotal regulatory role in the control of cell proliferation in the normal breast and breast cancer (BC). To identify genes with likely roles in proliferation control that are regulated by E and its downstream target c-myc, we compared transcript profiles of antiestrogens-arrested cells stimulated to reinitiate cell cycle progression by E treatment or c-myc induction. Approximately 2/3 of the probe sets significantly regulated by E (adjusted p < 0.01) increased in expression. Half of the E-regulated probe sets were also regulated by c-myc. Genes involved in cell growth, cell proliferation, and cell survival were over-represented in the E-regulated geneset. Analysis of selected candidates has identified a nucleolar protein whose expression is correlated with c-myc expression in BC cell lines. These data indicate that a significant component of E-induced mitogenesis is mediated by c-myc and that selected c-myc target genes may be surrogate markers of c-myc expression in BC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Estrogen Antagonists / pharmacology
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Estrogen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Zinc / pharmacology*

Substances

  • Biomarkers, Tumor
  • Estrogen Antagonists
  • Estrogens
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Zinc