The Role of c-Src Activation in Prostate Tumor Progression
M D ANDERSON CANCER CENTER HOUSTON TX
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DOD Award number DAMDl7-03-l-0484, The Role of c-Src Activation in Prostate Tumor Progression, has as its goal an understanding of the mechanisms of how activation of the protein tyrosine kinase, Src, contributes to prostate tumor progression and how Src regulation in host osteoclasts regulates metastatic growth of prostate tumor cells in the bone. In the first year of work, we have successfully developed cell lines from PC3 human prostate tumor cells that are constitutively increased in Src expression, or in which Src expression is induced by doxycyclin. Using these cells, we have demonstrated that increased Src activity leads to increased expression of vascular endothelial growth factor VEGF a novel finding implicating Src in promotion of angiogenesis by prostate tumor cells. We have further demonstrated that increased Src expression leads to increased tumorigenic growth in nude mice. Thus, we have provided new evidence that Src activation is important to prostate tumor progression. To examine the role of Src in growth of prostate tumor cells in the bone, we have begun to develop a Src-- nunu strain of mice. Breeding of these mice is underway and two generations of mice have been obtained. Continued studies should provide new insights into role of Src in both the tumor and host environment in promoting prostate tumor cell metastasis.
- Medicine and Medical Research