Role of Nip3 in Apoptosis and Chemoresponses of Breast Cancer Cells
Abstract
The overall objective of this project is to investigate the molecular mechanisms of Nip3's function in apoptosis and the role of Nip3 in chemoresponses of breast cancer cells. The first aim is to determine whether Nip3 acts directly or indirectly to induce cell death. The results showed that Nip3 does not directly induce cell death in yeast. Next, the role of Bax in Nip3 action was evaluated in the induction of yeast cell death. When Bax and Nip3 were co-transfected into yeast cells, no synergy between Bax and Nip3 in cell death induction was observed. Co-immunoprecipitation experiments also showed that there is no direct interaction between Bax and Nip3. Thus Nip3 induces apoptosis independent on Bax but requires additional factors. The potential Nip3 interacting proteins that collaborate with Nip3 to induce cell death in yeast is currently being investigated by yeast two-hybrid cloning. A parallel study of other BH3 domain containing protein has resulted the cloning of a new member of the Bcl-2 family, Bcl-GL. Over-expression of Bcl-G% or Bcl-05 in cells induced apoptosis, but Bcl-Gs was far more potent than Bcl-O%. Apoptosis induction by Bcl-Cl5 depended on the BH3 domain, and was suppressed by co-expression of anti-apoptotic Bcl-X% protein. Bcl-O gene is located in chromosome 12pl2, a region frequently subjected to loss of heterozygosity in cancer patients. The role of Bcl-O in breast cancer development and chemoresponse will be further studied.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396718
Entities
People
- Bin Guo
Organizations
- Sanford Burnham Prebys Medical Discovery Institute