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

• Published in: Advances in experimental medicine and biology Vol. 617; p. 445
• Main Authors: Musgrove, Elizabeth A, Sergio, C Marcelo, Anderson, Luke R, Inman, Claire K, McNeil, Catriona M, Alles, M Chehani, Gardiner-Garden, Margaret, Ormandy, Christopher J, Butt, Alison J, Sutherland, Robert L
• Format: Journal Article
• Language: English
• Published: United States 2008
• Subjects: 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; Receptors, Estrogen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Transcriptional Activation; Tumor Cells, Cultured; Zinc - pharmacology
• ISSN: 0065-2598
• DOI: 10.1007/978-0-387-69080-3_43

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.