Estrogen receptor (ER) regulates transcription in conjunction with the action of coregulatory molecules that interact with the receptor in a ligand-dependent fashion. The gene for one of these ER coregulators, AIB1, is amplified in a subset of human breast cancers and functions as an oncogene. Work from several labs including our own have implicated AIB1 and other coregulators in determining the tissue and tumor-specific activities of selective estrogen receptor modulators (SEiRMs) such as tamoxifen and as playing a role in tamoxifen resistance. Aromatase inhibitors (Al) have replaced tamoxifen as first-line endocrine therapy for post-menopausal women with advanced ER+ breast cancer and are rapidly replacing tamoxifen in early stage ER+ breast cancer as well. However, little is known concerning the mechanism underlying de novo resistance to Al therapy. We hypothesize that the levels and activity of A1B1 and other ER coregulators play a role in determining a tumor's response to Al therapy. We will test this hypothesis in cell-based models of estrogen deprivation, a transgenic mouse model of A1B1-dependent breast cancer, and in the pre-surgical setting in postmenopausal women with newly diagnosed ER+ breast cancer. These studies will facilitate the translation of progress in our basic understanding of the importance of coregulators in ER action to improvements in endocrine therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA089393-08
Application #
7550395
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
8
Fiscal Year
2007
Total Cost
$172,933
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Punglia, Rinaa S; Jiang, Wei; Lipsitz, Stuart R et al. (2018) Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery. Breast Cancer Res Treat 167:751-759
Liu, Hui; Murphy, Charles J; Karreth, Florian A et al. (2018) Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple-Negative Breast Cancer. Cancer Discov 8:354-369
Kabraji, Sheheryar; Ni, Jing; Lin, Nancy U et al. (2018) Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain? Clin Cancer Res 24:1795-1804
Asdourian, Maria S; Swaroop, Meyha N; Sayegh, Hoda E et al. (2017) Association Between Precautionary Behaviors and Breast Cancer-Related Lymphedema in Patients Undergoing Bilateral Surgery. J Clin Oncol 35:3934-3941
Sun, Fangdi; Skolny, Melissa N; Swaroop, Meyha N et al. (2016) The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema. Breast Cancer Res Treat 157:229-240
Ferguson, Chantal M; Swaroop, Meyha N; Horick, Nora et al. (2016) Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer. J Clin Oncol 34:691-8
Miller, Cynthia L; Colwell, Amy S; Horick, Nora et al. (2016) Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema Compared to Mastectomy Alone: A Prospective Cohort Study. Ann Surg 263:399-405
Sherr, Charles J; Beach, David; Shapiro, Geoffrey I (2016) Targeting CDK4 and CDK6: From Discovery to Therapy. Cancer Discov 6:353-67
Asdourian, Maria S; Skolny, Melissa N; Brunelle, Cheryl et al. (2016) Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis. Lancet Oncol 17:e392-405
Kochupurakkal, Bose S; Iglehart, J Dirk (2016) Identification of genes responsible for RelA-dependent proliferation arrest in human mammary epithelial cells conditionally expressing RelA. Genom Data 7:92-3

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