The long-term objectives of my Ph.D. thesis project is to define the pathophysiological mechanisms underlying tumor suppression mediated by Bin1 and the E2F1 transcription factor at the molecular and cellular levels. My preliminary results strongly suggest that Bin1 functionally interacts with E2F1 in LNCaP (where p53 is intact) and DU145 (where p53 is mutated) prostate cancer cell lines to reduce cell growth rate. I hypothesize that Bin1 plays a role in the E2Fl-dependent growth suppression independently of p53.
The specific aims of this proposed study are to determine whether Bin1 is necessary for E2Fl-dependent growth suppression and vice versa, and to define the role of Bin1 in apoptosis or senescence induced by E2F1. I also aim to assess whether p73, a p53 gene homologue and a direct transcriptional target of E2F1, is required for the growth suppression by Bin1. I wilt use colony formation assay, small-interfering RNA, and biochemical and molecular cell biological techniques using human cancer cell lines. Because neither apoptosis nor senescence mediated by E2F1 occurs naturally in cancer cells, the exact mechanism through which Bin1 and E2F1 act in cancer cells has emerged as a major question in cancer biology. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA110205-02
Application #
6952318
Study Section
Special Emphasis Panel (ZRG1-ONC-O (29))
Program Officer
Bini, Alessandra M
Project Start
2004-08-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$39,323
Indirect Cost
Name
Purdue University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Lundgaard, Greta L; Daniels, Natae E; Pyndiah, Slovénie et al. (2011) Identification of a novel effector domain of BIN1 for cancer suppression. J Cell Biochem 112:2992-3001
Pyndiah, Slovénie; Tanida, Satoshi; Ahmed, Kazi M et al. (2011) c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1: a mechanism by which cancer cells acquire cisplatin resistance. Sci Signal 4:ra19
Cassimere, E K; Pyndiah, S; Sakamuro, D (2009) The c-MYC-interacting proapoptotic tumor suppressor BIN1 is a transcriptional target for E2F1 in response to DNA damage. Cell Death Differ 16:1641-53