The overall goal of this proposal is to elucidate the precise role of the nuclear RARs in mediating the growth response of human breast cancer cells to retinoic acid.
The specific aims of this proposal are: 1) to determine if growth suppression of RA-sensitive cells can be modulated by changing the RAR profile in these cells; 2) to elucidate the molecular basis for the altered RAR profile in RA- resistant breast cancer cells; 3) to identify RAR/RXR tanscriptional targets which mediate the RA-dependent suppression of breast cancer cell growth; and 4) to examine the molecular mechanism by which these RAR/RXR transcriptional targets regulate RA-mediated growth suppression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK049045-01A1
Application #
2149609
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1995-08-01
Project End
1999-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Temple University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Le, Quan; Soprano, Dianne Robert; Soprano, Kenneth J (2002) Profiling of retinoid mediated gene expression in synchronized human SCC cells using Atlas human cDNA expression arrays. J Cell Physiol 190:345-55
Zhang, D; Vuocolo, S; Masciullo, V et al. (2001) Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression. Oncogene 20:7935-44
Duker, N J; Sperling, J; Soprano, K J et al. (2001) beta-Amyloid protein induces the formation of purine dimers in cellular DNA. J Cell Biochem 81:393-400
Holmes, W F; Dawson, M I; Soprano, R D et al. (2000) Induction of apoptosis in ovarian carcinoma cells by AHPN/CD437 is mediated by retinoic acid receptors. J Cell Physiol 185:61-7
Le, Q; Dawson, M I; Soprano, D R et al. (2000) Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids. Oncogene 19:1457-65
Zhang, D; Holmes, W F; Wu, S et al. (2000) Retinoids and ovarian cancer. J Cell Physiol 185:20-Jan
Wu, S; Zhang, D; Zhang, Z P et al. (1998) Critical role of both retinoid nuclear receptors and retinoid-X-receptors in mediating growth inhibition of ovarian cancer cells by all-trans retinoic acid. Oncogene 17:2839-49
Wu, S; Zhang, D; Donigan, A et al. (1998) Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth. J Cell Biochem 68:378-88
Wu, S; Donigan, A; Platsoucas, C D et al. (1997) All-trans-retinoic acid blocks cell cycle progression of human ovarian adenocarcinoma cells at late G1. Exp Cell Res 232:277-86
Wu, S; Zhang, Z P; Zhang, D et al. (1997) Reduction of both RAR and RXR levels is required to maximally alter sensitivity of CA-OV3 ovarian tumor cells to growth suppression by all-trans-retinoic acid. Exp Cell Res 237:118-26

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