This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lahusen, T. Articles by Riegel, A. T. Search for Related Content PubMed PubMed Citation Articles by Lahusen, T. Articles by Riegel, A. T.

Epidermal Growth Factor Receptor Tyrosine Phosphorylation and Signaling Controlled by a Nuclear Receptor Coactivator, Amplified in Breast Cancer 1

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia

Requests for reprints: Anna T. Riegel, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Research Building, 3970 Reservoir Road, NRB E311, Washington, DC 20057. Phone: 202-687-1479; Fax: 202-687-4821; E-mail: ariege01{at}georgetown.edu.

The steroid receptor coactivator amplified in breast cancer 1 (AIB1) as well as epidermal growth factor receptor (EGFR) family members are frequently overexpressed in epithelial tumors, and their expression is associated with poor prognosis. However, a direct role of AIB1 in EGF signaling has not been determined. To address this, we reduced endogenous AIB1 levels using RNA interference in lung, breast, and pancreatic cancer cell lines. We found that a knockdown of AIB1 levels resulted in a loss of the growth response of these cell lines to EGF. Further analysis revealed that the depletion of AIB1 reduced tyrosine phosphorylation of EGFR at multiple residues both at autophosphorylation and Src kinase phosphorylation sites. AIB1 knockdown did not affect tyrosine phosphorylation of the receptor tyrosine kinases, platelet-derived growth factor receptor and HER3, or overall tyrosine phosphorylation of cellular proteins. However, EGF-dependent phosphorylation of HER2 was decreased. EGFR levels and membrane trafficking were not changed by AIB1 depletion, but there was less recruitment of Src homology 2 domain-containing proteins to the EGFR. This led to a substantial reduction in EGF-induced phosphorylation of signal transducers and activators of transcription 5 and c-Jun NH₂-terminal kinase but no significant change in the activation of AKT. Vanadate treatment of cells revealed that the reduction in EGFR tyrosine phosphorylation is dependent in part on changes in cellular phosphatase activity. We propose that a portion of the oncogenic effect of AIB1 could be through control of EGFR and HER2 activity and subsequent modulation of cellular signaling pathways. [Cancer Res 2007;67(15):7256–65]

This article has been cited by other articles:

				A. S. Oh, J. T. Lahusen, C. D. Chien, M. P. Fereshteh, X. Zhang, S. Dakshanamurthy, J. Xu, B. L. Kagan, A. Wellstein, and A. T. Riegel Tyrosine Phosphorylation of the Nuclear Receptor Coactivator AIB1/SRC-3 Is Enhanced by Abl Kinase and Is Required for Its Activity in Cancer Cells Mol. Cell. Biol., November 1, 2008; 28(21): 6580 - 6593. [Abstract] [Full Text] [PDF]

				L. Qin, L. Liao, A. Redmond, L. Young, Y. Yuan, H. Chen, B. W. O'Malley, and J. Xu The AIB1 Oncogene Promotes Breast Cancer Metastasis by Activation of PEA3-Mediated Matrix Metalloproteinase 2 (MMP2) and MMP9 Expression Mol. Cell. Biol., October 1, 2008; 28(19): 5937 - 5950. [Abstract] [Full Text] [PDF]

				H. Yamashita, M. Nishio, T. Toyama, H. Sugiura, N. Kondo, S. Kobayashi, Y. Fujii, and H. Iwase Low phosphorylation of estrogen receptor {alpha} (ER{alpha}) serine 118 and high phosphorylation of ER{alpha} serine 167 improve survival in ER-positive breast cancer Endocr. Relat. Cancer, September 1, 2008; 15(3): 755 - 763. [Abstract] [Full Text] [PDF]

				M. P. Fereshteh, M. T. Tilli, S. E. Kim, J. Xu, B. W. O'Malley, A. Wellstein, P. A. Furth, and A. T. Riegel The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for Neu (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice Cancer Res., May 15, 2008; 68(10): 3697 - 3706. [Abstract] [Full Text] [PDF]