| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Geldanamycin(GA) was administered to several strains highly expressive of various HER-2 to find whether GA, an Hsp90-selective inhibitor, can be administered to ovarian cancer as a molecular-targeted therapy. For a medium-to-high degree of expression of HER-2, GA administration resulted in a reduction in protein expression and an evident suppression of cell proliferation. On the other hand, Hsp70, in cooperation with Hsp60 and others, performed a protein chaperon function for Hsp90. It has been known that Hsp70 expression is exaggerated in conditions such as ovarian and breast tumors and osteosarcoma. We have conducted a proteomics analysis of the protein group that had undergone changes in the Ga-treated and control groups, in comparison with the ovarian cancer with high HER-2 expression, and learned that the Hsp70 content increased significantly after GA administration, in comparison with the control. It was presumed that GA administration releases Hsp90 from its bond with HSF-1(heat
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shock transcription factor 1) ; HSF-1 is activated, in turn causing the Hsp gene activation. In other words, one expects that the cancer cells cause the Hsp70 content to increase to cover the damage, in an effort to survive the onslaught by antineoplastic agent administration. The increase in Hsp70 is ultimately linked to the resistance to apoptosis and even to the development of drug resistance of these cells. Currently, a study is underway not only on the Hsp70 function as a molecular chaperon but also on its signal transduction function in apoptosis-suppressive effects so that the results may lead to a new molecular targeted therapy mainly for ovarian cancer. Currently, a study is being conducted to evaluate the extent of involvement of Hsp70 in proteolysis by preparing RNAi of Hsp70 and introducing the gene into the cells. Also included : to discover whether the addition of an Hsp70 inhibitor to a strain with a high expression of Hsp70 will resolve the anti-apoptosis action and ultimately result in overcoming the resistance to antineoplastic agents. Less
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