The nuclear receptor coactivator AIB1 mediates insulin-like growth factor I-induced phenotypic changes in human breast cancer cells.
The nuclear receptor coactivator AIB1 (amplified in breast cancer 1) is overexpressed in human breast cancers and is required for estrogen signaling. However, the role of AIB1 in breast cancer etiology is not known. Here, we show that AIB1 is rate-limiting for insulin-like growth factor I (IGF-I)-dependent phenotypic changes and gene expression in human breast cancer cells. Reduction of endogenous AIB1 levels by small interfering RNA in MCF-7 breast cancer cells prevented IGF-I-stimulated anchorage-independent growth by reducing IGF-I-dependent anti-anoikis. cDNA array and immunoblot analysis of gene expression revealed that reduction in AIB1 levels led to a significant decrease in the expression of several genes controlling the cell cycle and apoptosis. These AIB1-dependent changes were also observed in the presence of estrogen antagonist and were corroborated in the estrogen receptor-negative cell line MDA MB-231. AIB1 reduction decreased the expression of the IGF-I receptor and IRS-1 in MCF-7 but not in MDA MB-231 cells. IGF-I-stimulated activation of AKT was reduced by AIB1 small interfering RNA treatment, whereas mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) activation by IGF-I was unaffected. We conclude that AIB1 is required for IGF-I-induced proliferation, signaling, cell survival, and gene expression in human breast cancer cells, independent of its role in estrogen receptor signaling.
Oh
Annabell
A
Department of Oncology, Vincent T. Lombardi Cancer Center, Georgetown University, Washington, District of Columbia 20057, USA.
List
Heinz-Joachim
HJ
Reiter
Ronald
R
Mani
Aparna
A
Zhang
Ying
Y
Gehan
Edmund
E
Wellstein
Anton
A
Riegel
Anna T
AT
D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D056921:Nuclear Receptor Coactivator 3; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases