Abstract

The investigators hypothesize that a complex combination of regulatory mechanisms is responsible for the low level of EGFR expression in ER+ breast cancer cells and that alterations in these mechanisms results in EGFR up- regulation during the progression to hormone-independence, and ultimately the overexpression of EGFR in ER- breast cancer cells. Using the available molecular biological techniques and the resources of the Lombardi Cancer Center, the investigators proposed to study three specific aims: 1) to determine the mechanisms by which low basallevels of EGFR are maintained in ER+ breast cancer cells, 2) to determine the mechanisms by which overexpression of EGFR occurs in ER- breast cancer cells and 3) to define the role of EGFR in the progression of breast cancer to hormone-independence. The results of the study may provide a specific target for the treatment and prevention of hormone-independent breast cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA055677-06
Application #
2517565
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1992-09-01
Project End
1998-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

McGaffin, Kenneth R; Acktinson, Lisa E; Chrysogelos, Susan A (2004) Growth and EGFR regulation in breast cancer cells by vitamin D and retinoid compounds. Breast Cancer Res Treat 86:55-73
Wilson, Melissa A; Chrysogelos, Susan A (2002) Identification and characterization of a negative regulatory element within the epidermal growth factor receptor gene first intron in hormone-dependent breast cancer cells. J Cell Biochem 85:601-14
McInerney, J M; Wilson, M A; Strand, K J et al. (2001) A strong intronic enhancer element of the EGFR gene is preferentially active in high EGFR expressing breast cancer cells. J Cell Biochem 80:538-49
Yarden, R I; Wilson, M A; Chrysogelos, S A (2001) Estrogen suppression of EGFR expression in breast cancer cells: a possible mechanism to modulate growth. J Cell Biochem Suppl Suppl 36:232-46
Yarden, R I; Lauber, A H; El-Ashry, D et al. (1996) Bimodal regulation of epidermal growth factor receptor by estrogen in breast cancer cells. Endocrinology 137:2739-47
Murphey, J M; Chrysogelos, S A (1995) Direct measurement of transfection efficiency in transient transfection assays. Biotechniques 18:967-9
Chrysogelos, S A; Yarden, R I; Lauber, A H et al. (1994) Mechanisms of EGF receptor regulation in breast cancer cells. Breast Cancer Res Treat 31:227-36
Chrysogelos, S A; Dickson, R B (1994) EGF receptor expression, regulation, and function in breast cancer. Breast Cancer Res Treat 29:29-40
Chrysogelos, S A (1993) Chromatin structure of the EGFR gene suggests a role for intron 1 sequences in its regulation in breast cancer cells. Nucleic Acids Res 21:5736-41