Abstract

The proposed studies address molecular mechanisms that may explain tissue-specific and gene- specific regulation by progestins.
Aim 1 is to assess the functional differences between A- and B-receptors in breast and endometrial cells.
Aim 2 is to investigate BUS (the B-upstream segment) as a third transcriptional activation domain unique to B-receptors. Finally, Aim 3 is to determine the mechanisms of TAF-3 action in the BUS segment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK048238-05S1
Application #
6151802
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Margolis, Ronald N
Project Start
1994-09-01
Project End
2000-03-31
Budget Start
1998-09-18
Budget End
2000-03-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Hopp, Torsten A; Weiss, Heidi L; Hilsenbeck, Susan G et al. (2004) Breast cancer patients with progesterone receptor PR-A-rich tumors have poorer disease-free survival rates. Clin Cancer Res 10:2751-60
Sartorius, Carol A; Shen, Tianjie; Horwitz, Kathryn B (2003) Progesterone receptors A and B differentially affect the growth of estrogen-dependent human breast tumor xenografts. Breast Cancer Res Treat 79:287-99
Takimoto, Glenn S; Tung, Lin; Abdel-Hafiz, Hany et al. (2003) Functional properties of the N-terminal region of progesterone receptors and their mechanistic relationship to structure. J Steroid Biochem Mol Biol 85:209-19
Richer, Jennifer K; Jacobsen, Britta M; Manning, Nicole G et al. (2002) Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. J Biol Chem 277:5209-18
Abdel-Hafiz, Hany; Takimoto, Glenn S; Tung, Lin et al. (2002) The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression. J Biol Chem 277:33950-6
Jacobsen, Britta M; Richer, Jennifer K; Schittone, Stephanie A et al. (2002) New human breast cancer cells to study progesterone receptor isoform ratio effects and ligand-independent gene regulation. J Biol Chem 277:27793-800
Tung, L; Shen, T; Abel, M G et al. (2001) Mapping the unique activation function 3 in the progesterone B-receptor upstream segment. Two LXXLL motifs and a tryptophan residue are required for activity. J Biol Chem 276:39843-51
Shen, T; Horwitz, K B; Lange, C A (2001) Transcriptional hyperactivity of human progesterone receptors is coupled to their ligand-dependent down-regulation by mitogen-activated protein kinase-dependent phosphorylation of serine 294. Mol Cell Biol 21:6122-31
Bain, D L; Franden, M A; McManaman, J L et al. (2001) The N-terminal region of human progesterone B-receptors: biophysical and biochemical comparison to A-receptors. J Biol Chem 276:23825-31
Bain, D L; Franden, M A; McManaman, J L et al. (2000) The N-terminal region of the human progesterone A-receptor. Structural analysis and the influence of the DNA binding domain. J Biol Chem 275:7313-20

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