Tumor suppressor gene networks as molecular targets for developing new cancer treatments

We have investigated the role of Rb in chromosome segregation based on the study of hsHec1p. Importantly, Hec-1 is a novel critical protein in M phase progression. We have shown that inactivation of Hec-1 by microinjection with anti-Hec-1 monoclonal antibodies led to cell death due to abnormal chromosomal segregation. Similarly, inactivation of scHEC-1 gene in yeast leads to lethal phenotype. In most cancer cell lines, expression of HEC-1 is highly elevated. Based on these preliminary results, we plan to address how Hec1p plays during chromosome segregation in mammalian cells and how we can use Hec-1 as a molecular target for developing small molecules that inactivate it function as potential therapeutic agents. On the other hand, germline mutation of the breast cancer susceptibility gene, BRCAl and 2, has been linked to familial breast cancer. To exploit the importance of this interaction toward the development of new anti-breast cancer agents, we plan to use this pathway as therapeutic targets. Disruption of the interaction between BRCA2 and Rad51 or BRCAl and RadSO complex will render the cancer cells sensitize to traditional chemotherapy or radiation therapy.