Down-regulation of programd cell death (apoptosis) and functional inactivation of tumor suppressors are the rate limited steps towards tumorigenesis. Enhancing survival functions by amplification of Bcl-2, PI-3 kinase, Protein kinase B (PKB/AKT) to repress apoptosis occurs in many human cancers. Functional inactivation of tumor suppressors, like p53, pTEN, and p14ARF takes place with high frequency (35-50%) in human tumors of the endometrium, brain, prostate, and others.
- Function of AKT in mitochondrial pathway of apoptosis
- Role of Erk activation in DNA damage checkpoint that plays a major role in preventing tumor formation
- Searching for proteins interacted with pTEN or p14ARF to modulate either positively or negatively on the functions of pTEN or p14ARF
Approaches of genetics, molecular biology, cellular biology, and biochemistry are explored to address the above questions, including generation of stable or inducible cell lines using plasmid and retrovirus, detection of protein-protein interaction and cell cycle progression.