Abstract

The objective of this application is to determine the mechanism by which retinoids inhibit the growth of ovarian cancer cells. It is proposed to: (1) Elucidate the important molecular events in the pathway by which AHPN induces apoptosis in ovarian carcinoma cells. More specifically, the role of the RARs and RXRs in AHPN induced apoptosis of ovarian carcinoma cells, and the importance and function of ligand binding to RAR-g in mediating the induction of apoptosis by AHPN, will be determined; and (2) Investigate the mechanism by which retinoid antagonism of AP-1 activity mediates the retinoid-dependent suppression of ovarian carcinoma cell growth. More specifically, RA mediated changes in expression and phosphorylation status of AP-1 components, the role of co- activators such as CBP and p300, and the use of RAR-b isoforms to map the sequences of RARs that are essential for this activity, will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA064945-06
Application #
6172337
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Forry, Suzanne L
Project Start
1994-08-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
6
Fiscal Year
2000
Total Cost
$192,810
Indirect Cost

  Institution

Name
Temple University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122

  Publications

Purev, Enkhtsetseg; Soprano, Dianne R; Soprano, Kenneth J (2011) PP2A interaction with Rb2/p130 mediates translocation of Rb2/p130 into the nucleus in all-trans retinoic acid-treated ovarian carcinoma cells. J Cell Physiol 226:1027-34
Acquafreda, Thais; Nunes, Fabio Daumas; Soprano, Dianne Robert et al. (2010) Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all-trans retinoic acid. J Cell Biochem 111:1437-44
Zhao, Jianhua; Zhang, Zhenping; Vucetic, Zivjena et al. (2009) HACE1: A novel repressor of RAR transcriptional activity. J Cell Biochem 107:482-93
Fields, Anthonise Louis; Soprano, Dianne Robert; Soprano, Kenneth J (2008) Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells. J Cell Physiol 217:77-85
Radu, Maria; Soprano, Dianne R; Soprano, Kenneth J (2008) S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian carcinoma cell lines. J Cell Physiol 217:558-68
Fields, Anthonise Louis; Soprano, Dianne Robert; Soprano, Kenneth J (2007) Retinoids in biological control and cancer. J Cell Biochem 102:886-98
Ravikumar, Sharada; Perez-Liz, Georgina; Del Vale, Luis et al. (2007) Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid. Cancer Res 67:9266-75
Jiang, Tianying; Soprano, Dianne Robert; Soprano, Kenneth J (2007) GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol 212:771-9
Purev, Enkhtsetseg; Giordano, Antonio; Soprano, Dianne Robert et al. (2006) Interaction of PP2A catalytic subunit with Rb2/p130 is required for all-trans retinoic acid suppression of ovarian carcinoma cell growth. J Cell Physiol 206:495-502
Soprano, K J; Purev, E; Vuocolo, S et al. (2006) Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid. Oncogene 25:5315-25

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