Adenovirus-Mediated p202 Gene Transfer in Breast Cancer Gene Therapy
Annual rept. 1 May 2003-30 Apr 2004
M D ANDERSON CANCER CENTER HOUSTON TX
Pagination or Media Count:
The HIN-200 family are IFN-inducible proteins that share a signature 200-amino acid motif of type a andor b. Three human IFI16, MNDA, and AIM2 and four mouse p202, p203, p204, and D3 HIN-200 family proteins have been identified. Genes encoding HIN-200 family proteins in both mouse and human are located at chromosome 1q21-23 and form a gene cluster. HIN-200 proteins are primarily nuclear proteins involved in transcriptional regulation of genes important for cell cycle control, differentiation, and apoptosis. Our previous studies have established that p202 suppressed tumor growth, reduced tumorigenicity, induced apoptosis, and suppressed metastasis and tumor angiogenesis of many human cancer cell lines. The main goal of this project is to study the anti-tumor activity of p202 aim 1, and the potential application to breast cancer gene therapy aim 2. Aim 3 is based on our recent discovery of a novel human HIN-200 gene, IFIX IFN-Inducible protein X. Our preliminary data showed the expression of IFIX is reduced in breast tumor tissues and breast cancer cell lines and that the enforced expression of IFIX in breast cancer cell lines reduces their growth and tumorigenicity. We also demonstrated the treatment efficacy of an IFIX-based gene therapy in an orthotopic breast cancer model. Together, we hypothesize that IFIX functions as a tumor suppressor and may be developed as a therapeutic agent in breast cancer treatment. The new aim will further test the above hypothesis.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research