AIB1 enhances estrogen-dependent induction of cyclin D1 expression.
AIB1 was isolated as a gene amplified in breast cancer and encodes a protein that acts as a steroid receptor coactivator. The role of steroid receptor coactivators such as AIB1 in breast cancer development is not clear. It is possible that AIB1 cooperates with estrogen receptor alpha in regulating estrogen-dependent cell proliferation. Ectopic expression of the estrogen receptor alpha in different cell lines does not confer estrogen-induced proliferation. This inability of the estrogen receptor to drive proliferation has been recently correlated with a lack of estrogen-dependent cyclin D1 expression in cells engineered to express the estrogen receptor. In this study, we evaluated whether high levels of AIB1 enable the estrogen receptor to direct the transcription of cyclin D1. We show here that AIB1 and other steroid receptor coactivators can enhance the functional interaction of the estrogen receptor with the cyclin D1 promoter. Increases of AIB1 levels in breast cancer cells by amplification and/or overexpression may represent one way to confer estrogen-dependent mitogenic stimulation to breast cancer cells.
Planas-Silva
M D
MD
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Shang
Y
Y
Donaher
J L
JL
Brown
M
M
Weinberg
R A
RA
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005786:Gene Expression Regulation; D019940:Genes, bcl-1 / Q000502:physiology; D051548:Histone Acetyltransferases; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004967:Estrogens; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D014157:Transcription Factors; D019938:Cyclin D1; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3