Identification of downstream targets of estrogen and c-myc in breast cancer cells.
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.
Musgrove
Elizabeth A
EA
Cancer Research Program, Garvan Institute, Darlinghurst, Sydney, Australia.
Sergio
C Marcelo
CM
Anderson
Luke R
LR
Inman
Claire K
CK
McNeil
Catriona M
CM
Alles
M Chehani
MC
Gardiner-Garden
Margaret
M
Ormandy
Christopher J
CJ
Butt
Alison J
AJ
Sutherland
Robert L
RL
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology*
D014408:Biomarkers, Tumor; D004965:Estrogen Antagonists; D004967:Estrogens; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D015032:Zinc