Phenotypic alterations in breast cancer cells overexpressing the nuclear receptor co-activator AIB1.
BACKGROUND
Estrogen signaling plays a critical role in a number of normal physiological processes and has important implications in the treatment of breast cancer. The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently amplified and overexpressed in human breast cancer and has been shown to enhance estrogen-dependent transactivation.


METHODS
To better understand the molecular and physiological consequences of AIB1 overexpression in breast cancer cells, an AIB1 cDNA was transfected into the low AIB1 expressing, estrogen-receptor (ER) negative breast cancer cell line, MDA-MB-436. The features of a derivative cell line, designated 436.1, which expresses high levels of AIB1, are described and compared with the parental cell line.


RESULTS
A significant increase in the levels of CREB binding protein (CBP) was observed in 436.1 cells and immunofluorescent staining revealed altered AIB1 and CBP staining patterns compared to the parental cells. Further, transient transfection assays demonstrated that the overall estrogen-dependent transactivation in 436.1 cells is approximately 20-fold higher than the parental cells and the estrogen dose-response curve is repositioned to the right. Finally, cDNA microarray analysis of approximately 7,100 cDNAs identified a number of differentially expressed genes in the 436.1 cells.


CONCLUSIONS
These observations lend insight into downstream signaling pathways that are influenced by AIB1.
Anzick
Sarah L
SL
Cancer Genetics Branch, NHGRI, National Institutes of Health, Bethesda, MD 20892, USA. sanzick@nhgri.nih.gov
Azorsa
David O
DO
Simons
S Stoney
SS
Meltzer
Paul S
PS
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D050882:CREB-Binding Protein; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D056921:Nuclear Receptor Coactivator 3