| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
Departments of 1 Oncology and 2 Pharmacology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia and 3 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas
Requests for reprints: Anna T. Riegel, Department of Oncology, Lombardi Comprehensive Cancer Center Research Building, Georgetown University, 3970 Reservoir Road, NRB E311, Washington, DC 20057. Phone: 202-687-1479; Fax: 202-687-4821; E-mail: ariege01{at}georgetown.edu.
Key Words: AIB1/SRC-3 • breast cancer • HER2/Neu/ErbB2
Overexpression of the oncogene amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis in mice. In breast cancer, high levels of AIB1/SRC-3 and the growth factor receptor HER2/neu predict resistance to endocrine therapy and poor outcome. However, a mechanistic relationship between AIB1/SRC-3 and HER2/neu in the development of breast cancer has not been shown. Here, we show that deletion of one allele of SRC-3 significantly delays Neu-induced mammary tumor development in mice. Homozygous deletion of SRC-3 in mice completely prevents Neu-induced tumor formation. By ages 3 to 4 months, Neu/SRC-3+/– mice exhibit a noticeable reduction in lateral side-bud formation, accompanied by reduced cellular levels of phosphorylated Neu compared with Neu/SRC-3wt mice. In Neu-induced tumors, high levels of SRC-3, phosphorylated Neu, cyclin D1, cyclin E, and proliferating cell nuclear antigen expression are observed, accompanied by activation of the AKT and c-Jun NH2 kinase (JNK) signaling pathways. In comparison, phosphorylated Neu, cyclin D1, and cyclin E are significantly decreased in Neu/SRC-3+/– tumors, proliferation is reduced, and AKT and JNK activation is barely detectable. Our data indicate that AIB1/SRC-3 is required for HER2/neu oncogenic activity and for the phosphorylation and activation of the HER2/neu receptor. We predict that reducing AIB1/SRC-3 levels or activity in the mammary epithelium could potentiate therapies aimed at inhibiting HER2/neu signaling in breast cancer. [Cancer Res 2008;68(10):3697–706]
This article has been cited by other articles:
|
|
 |
|
  S. Alkner, P.-O. Bendahl, D. Grabau, K. Lovgren, O. Stal, L. Ryden, M. Ferno, and on behalf of the South Swedish and South-East Swed AIB1 is a predictive factor for tamoxifen response in premenopausal women Ann. Onc., July 23, 2009; (2009) mdp293v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Redmond, F. T. Bane, A. T. Stafford, M. McIlroy, M. F. Dillon, T. B. Crotty, A. D. Hill, and L. S. Young Coassociation of Estrogen Receptor and p160 Proteins Predicts Resistance to Endocrine Treatment; SRC-1 is an Independent Predictor of Breast Cancer Recurrence Clin. Cancer Res., March 15, 2009; 15(6): 2098 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wang, Y. Yuan, L. Liao, S.-Q. Kuang, J. C.-Y. Tien, B. W. O'Malley, and J. Xu Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation PNAS, January 6, 2009; 106(1): 151 - 156. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
