| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Takao Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (10304825)
KATO Kiyoko Medical Institute of Bioregulation Kyushu Univ.Assistant Professor, 生体防御医学研究所, 助手 (10253527)
KATO Hidenori Medical Institute of Bioregulation Kyushu Univ.Assistant Professor, 生体防御医学研究所, 講師 (60214392)
WAKE Norio Medical Institute of Bioregulation Kyushu Univ.Professor, 生体防御医学研究所, 教授 (50158606)
有馬 隆博 九州大学, 生体防御医学研究所, 助手 (80253532)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
1.Transcriptional repression of SM alpha actin by HPV16E7. We demonstrated that HPV16E7 (E7) could repress the expression of SM alpha actin previously, Expression of SM alpha actin was activated by transcriptional factor Myo D, which was regulated by Rb and c-jun. Rb enhanced transcriptional activity of Myo D, whereas c-jun repressed its expression. E7 could bind both Rb and c-jun through its distinct domain, respectively, In this study, we revealed that mutant E7 capable of binding to Rb but not c-jun lost its transrepression activity of SM alpha actin expression. However deletion mutant of c-jun lacking AP-1 activity but remaining binding ability to E7 could not restore the SM alpha actin expression in E7 expressing cells. These datas suggested that interaction with c-jun and E7 was essential for transrepression activity of SM alpha actin, which was not associateal with AP-1 activity.
2.Possible interaction of E7 and bcl-2. : We have established immortalized rat embryonal fibroblasts
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(REF) by E7 (TF-1), in which expression level of bcl-2 protein was elevated. In order to determine potential role of E7 to induce bcl-2 protein, other rodent fibroblasts cell line, NIH3T3, 3Y1 and Rat1a, were transfected with E7, In these cells, E7 could not induce bcl-2 protein expression, suggesting that elevated expression of bcl-2 protein in TF-1 might be acquired during immortalizing process. We are flow investigating if bcl-2 can protect apoptosis by E7 during immortalization process of primary cultured REF.
3.Genetic diagnosis of metastasis in cervical cancer patients. We analyzed the existence of HPV genome in surgical resected lymph node by PCR-southern blot method. Ten cases out of 64 cases were revealed histologically metastasis positive. In all these cases, HPV genome were detected, HPV genome were also detected in 45 cases of 54 cases (83%) which were metastasis negative diagnosed by histological examination. These results suggested extreme higher sensitivity of genetic diagnosis compared with histological diagnosis. We are now determining prognosis of these patients to confirm clinical usefullness for genetic diagnosis of metastasis in cervical cancer patients. Less
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