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. ? ?
| 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 |
