The applicant has generated a series of cellular models that mimic breast cancer's progression from estrogen (E2) dependence to E2-independence and to anti-estrogen cross resistance. Using 2-D gel analysis, the applicant has identified nucleophosmin (NPM) as a protein associated with acquired E2-independence. Data suggests that NPM levels are 8-fold higher in E2-independent and antiestrogen cross resistant cells when compared with E2-dependent cells. NPM can be detected in primary breast cancer specimens, and auto-antibodies to NPM can be detected in the sera of breast cancer patients. The applicant has three hypotheses: 1) elevated NPM expression and/or its state of phosphorylation are necessary and/or sufficient to confer the phenotypes associated with its expression; 2) the production of NPM autoantibody predicts recurrence or identifies tamoxifen non-responders; and 3) NPM levels in primary breast cancer specimens has prognostic significance. To test these hypotheses, three aims are proposed that will determine 1) the effects of overexpression and decrease expression of NPM on E2-independence and antiestrogen cross resistance, 2) NPM phosphorylation patterns in the various phenotypes, and 3) the predictive power of NPM and its autoantibodies using both retrospective and prospective studies of human clinical specimens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA058022-06
Application #
2467950
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Longfellow, David G
Project Start
1992-08-01
Project End
2001-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Georgetown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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