Abstract

Preliminary experiments, Ets2 is essential for very early mouse development and that mutant forms of Ets transcription factors may/suggest suppress Ras transformation of normal cells. The applicant proposes to investigate the importance of the Ras pathway activation of Ets2 during mouse development by extending gene targeting. In addition, he will investigate the mechanism of the suppression and reversal of Ras induced cellular transformation by stable expression in cell lines of three different types of dominant Ets mutants which either inhibit Ets transcriptional function or specifically repress or activate Ets-dependent gene expression. It will further be determined if the transformed phenotypes of human breast, ovarian and prostate carcinoma cell lines can be reversed by stable expression of these Ets dominant mutants. Finally, the possible activation of Ets transcription factor activities in transganic mouse tumors will be evaluated. The applicant feels that these studies will provide important information on the role of Ets transcription factors during development and carcinogenesis and may lead to a strategy of intervention applicable to cancers caused by multiple types of non-nuclear oncogenes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA074547-02
Application #
2683720
Study Section
Special Emphasis Panel (ZRG2-MEP (02))
Program Officer
Marks, Cheryl L
Project Start
1997-06-02
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Wen, Fang; Tynan, John A; Cecena, Grace et al. (2007) Ets2 is required for trophoblast stem cell self-renewal. Dev Biol 312:284-99
West, Howard L; Franklin, Wilbur A; McCoy, Jason et al. (2006) Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest Oncology Group Study S0126. J Clin Oncol 24:1807-13
Tynan, John A; Wen, Fang; Muller, William J et al. (2005) Ets2-dependent microenvironmental support of mouse mammary tumors. Oncogene 24:6870-6
Liu, Mei; Howes, Amy; Lesperance, Jacqueline et al. (2005) Antitumor activity of rapamycin in a transgenic mouse model of ErbB2-dependent human breast cancer. Cancer Res 65:5325-36
Wei, Guo; Guo, Jianping; Doseff, Andrea I et al. (2004) Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. J Immunol 173:1374-9
Galang, Christina K; Muller, William J; Foos, Gabriele et al. (2004) Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors. J Biol Chem 279:11281-92
Hever, Aniko; Oshima, Robert G; Hauser, Craig A (2003) Ets2 is not required for Ras or Neu/ErbB-2 mediated cellular transformation in vitro. Exp Cell Res 290:132-43
Man, Albert K; Young, Lawrence J T; Tynan, John A et al. (2003) Ets2-dependent stromal regulation of mouse mammary tumors. Mol Cell Biol 23:8614-25
Foos, G; Galang, C K; Zheng, C F et al. (2001) Ras signaling to transcription activation: analysis with GAL4 fusion proteins. Methods Enzymol 333:61-73
Foos, G; Hauser, C A (2000) Altered Ets transcription factor activity in prostate tumor cells inhibits anchorage-independent growth, survival, and invasiveness. Oncogene 19:5507-16

Showing the most recent 10 out of 11 publications