SOGA Norihito Mie University, school of medicine, Department of Urology, Assistant Professor, 医学部附属病院, 助手 (60332714)
SUGIMURA Yoshiki Mie University, school of medicine, Department of Urology, Professor, 医学部, 教授 (90179151)
木瀬 英明 三重大学, 医学部附属病院, 助手 (80293786)
|Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 2004 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2003 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 2002 : ¥1,600,000 (Direct Cost : ¥1,600,000)
According to our results in vitro, significant differences was recognized on the activities of Rac, in prostate cancer cell lines, respectively. Especially, PC3 and DU145, androgen independent cells lines, had high activity of Rac, comparing with LNcap, androgen dependent cell line. Thus, high levels of Rac influenced the cancer characters, consisted of the cell proliferation, invasion and met static activity. Growth factor, through tyrosine kinase receptor, increased the Rac activity, time dependency, reached to the maximum level, on one hour exposure.
On the other hand, in PC3 and DU145, the induction with transient dominant negative Rac, eliminated Rac activity, contributed to the decreasing motility. These data elucidated that, Rac GTPase should be the key modulator, managing the motility in prostate cancer cell lines. Now, we are preparing for the high incident recombinant protein delivery system, based on adeno virus system, Tat protein and tetracycline system, but cannot be established for the stable induction, unfortunately.
For the future strategy, we start to evaluate the motility, related to the invasive function and proliferation, approaching from not only endogenous protein activity, but also interaction with external stimulator.
We have plan to decide the role of Rho GTPase, stimulated by VEGF, (through tyrosine kinase receptor), and external cellular matrix, (through integrin), respectively and interaction.