Abstract

Early Life Estrogenicity and Mammary Cancer Risk. While the timing of estrogen exposures has profound and often opposing effects on breast cancer suscepfibility, the molecular changes and programming that are altered by these exposures are almost entirely unknown. Dr. Hilakivi-Clarke and her team will focus on identifying key transcription factor-based signaling associated with increased mammary cancer risk in the mammary glands of rodents exposed to an elevated estrogenic environment in utero. We will determine the effects of these exposures on altering the sensitivity of the adult gland to E2, and on the endocrine responsiveness of mammary tumors arising in these glands. Data from these studies will be used to build computational models of ER-driven signaling associated with the effects of estrogens on increasing mammary gland susceptibility to neoplastic transformation and on endocrine responsiveness of mammary tumors. These data will also provide and unique powerful insights into the modeling in Projects 1 and 2.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA149147-05
Application #
8627142
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$77,623
Indirect Cost

  Institution

Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong et al. (2018) Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities. Mol Cell Endocrinol 471:105-117
Wärri, Anni; Cook, Katherine L; Hu, Rong et al. (2018) Autophagy and unfolded protein response (UPR) regulate mammary gland involution by restraining apoptosis-driven irreversible changes. Cell Death Discov 4:40
Shi, Xu; Wang, Xiao; Wang, Tian-Li et al. (2018) SparseIso: a novel Bayesian approach to identify alternatively spliced isoforms from RNA-seq data. Bioinformatics 34:56-63
Varghese, Rency S; Zuo, Yiming; Zhao, Yi et al. (2017) Protein network construction using reverse phase protein array data. Methods 124:89-99
Zhang, Xiyuan; Cook, Katherine L; Warri, Anni et al. (2017) Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats. Clin Cancer Res 23:814-824
Zhang, Yong-Wei; Nasto, Rochelle E; Jablonski, Sandra A et al. (2017) RNA Interference Screening to Identify Proliferation Determinants in Breast Cancer Cells. Bio Protoc 7:
Beck, Tim N; Smith, Chad H; Flieder, Douglas B et al. (2017) Head and neck squamous cell carcinoma: Ambiguous human papillomavirus status, elevated p16, and deleted retinoblastoma 1. Head Neck 39:E34-E39
Chen, Xi; Shi, Xu; Hilakivi-Clarke, Leena et al. (2017) PSSV: a novel pattern-based probabilistic approach for somatic structural variation identification. Bioinformatics 33:177-183
Sumis, Allison; Cook, Katherine L; Andrade, Fabia O et al. (2016) Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk. Endocr Relat Cancer 23:839-56
Beck, Tim N; Georgopoulos, Rachel; Shagisultanova, Elena I et al. (2016) EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer. Mol Cancer Ther 15:2486-2497

Showing the most recent 10 out of 107 publications