Aggressive and unfortunately numerous in the clinic, glioblastoma multiforme is a common form of primary brain tumor, necessitating the development of novel therapies to combat its relentless disease process. Preliminary results from our lab show that downregulation of Activating Transcription Factor 5 (ATF5), a cAMP response element binding protein, suppresses proliferation in cell culture. We will determine whether or not loss of function of ATF5 will reduce their proliferation and trigger apoptosis in tumors of transgenic mice that overexpress dominant negative (d/n) ATF5 transgene through an inducible TetO promoter. We hypothesize that loss of endogenous ATF5 activity in the context of cancer will demonstrate its potential as a novel prospective therapeutic target for anti-neoplastic agents, since ATF5 is found in most cancers including glioblastoma. Artificial induction of tumors through two routes of tumorigenesis will be created by retroviral injection of PDGF to demonstrate an amplified growth factor pathway, and by ethylnitrosourea (END) to simulate environmental exposure to a carcinogen. Our expectation is that its expression will result in destruction of tumor cells in both populations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA123711-02
Application #
7317802
Study Section
Special Emphasis Panel (ZRG1-EMNR-E (29))
Program Officer
Bini, Alessandra M
Project Start
2006-12-01
Project End
2009-06-16
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
2
Fiscal Year
2008
Total Cost
$30,513
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Cates, Charles C; Arias, Angelo D; Nakayama Wong, Lynn S et al. (2016) Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide. Oncotarget 7:12718-30
Arias, A; Lamé, M W; Santarelli, L et al. (2012) Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas. Oncogene 31:739-51