ERalpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis.
Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ERalpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ERalpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ERalpha. Similar to ERalpha, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ERalpha-CITED1 co-regulated signalling pathway in breast tumours can indicate good prognosis.
McBryan
J
J
UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Ireland.
Howlin
J
J
Kenny
P A
PA
Shioda
T
T
Martin
F
F
D066258:Amphiregulin; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D066255:EGF Family of Proteins; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008321:Mammary Glands, Animal / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D020218:Response Elements; D015534:Trans-Activators / Q000235:genetics*
C587848:AREG protein, human; D066258:Amphiregulin; D051017:Apoptosis Regulatory Proteins; C587849:Areg protein, mouse; C102208:Cited1 protein, mouse; D066255:EGF Family of Proteins; D047628:Estrogen Receptor alpha; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C114997:STC2 protein, human; C485438:Stc2 protein, mouse; D015534:Trans-Activators