1998 Fiscal Year Final Research Report Summary
Research on tumor-suppressive activity of apoptosis-related cysteine proteinase ICH-1
| Project/Area Number |
09680711
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Chiba University |
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Principal Investigator |
HIWASA Takaki Chiba University, School of Medicine, Lecturer, 医学部, 講師 (30260251)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWARA Akira Chiba Cancer Canter Research Institute, Division of Biochemistry, Head, 生化学研究部, 部長 (50117181)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Apoptosis / Protease / Caspase / Cancer |
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| Research Abstract |
Although it is generally accepted that caspase family proteases play central roles in induction of apoptosis, their other biological activity remains to be proved. Therefore, we have transfected cDNAs of caspase-1 (ICE), 2 (ICH-1) and 3 (CPP32) into Ha-ras-transformed NIH3T3 cells and investigated the effects after induction of their expression. High expression of these proteases alone did not result in apoptosis-like cell death. However, morphological reversion was frequently observed in clones which overexpressed caspase-2. The reversion was well correlated to the expression level of caspase-2. Moreover, the reverted clones lost the ability of anchorage-independent growth in soft agar medium. These results suggest that caspase-2 possesses the tumor suppressive activity toward Ha-ras-transformed cells. Similar effects of caspase-2 were also observed for v-src-transformed NIH3T3 cells but not for Ki-ras-transformed cells. Thus, caspase-2 may affect a signal transduction pathway which is specific for Src and Ha-Ras. Further western blot analysis showed that the expression level of Ha-Ras was reduced in caspase-2-producing cells. In vitro incubation of cell extract of Ha-ras-transformed cells resulted in degradation of Ha-Ras protein. Th is degradation was completely suppressed in the presence of caspase inhibitors. Taken together, it is plausible that caspase-2 induced reversion of transformed cells by stimulating the degradation of Ha-Ras protein.
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[Publications] Hiwasa, T., Kondo, K., Hishiki, T., Koshizawa, S., Umezawa, K.and Nakagawara, A.: "GDNF-induced neurite formation was stimulated by protein kinase inhibitors and suppressed by Ras inhibitors." Neurosci.Lett.238. 115-118 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakagawara, A., Nakamura, Y., Ikeda, H., Hiwaza, T., Kuida, K,Su, M.S-S., Zhao, H., Cnann, A.and Sakiyama, S.: "High levels of expression and nuclear localization of interleukin-1beta converting enzyme (ICE) and CPP32 in favorable human neuroblastmas." Cancer Res.57. 4578-4584 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Ikeda, H., Nakamura, Y., Hiwasa, T., Sakiyama, S., Kuida, K., Su, M.S.and Nakagawara, A.: "Interleukin-1beta converting enzyme (ICE) is preferentially expressed in neuroblastomas with favourable prognosis." Eur.J.Cancer. 33. 2081-2083 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Hiwasa, T., Nakamura, Y., Ozaki, T., Kondo, K., Saido, T., Nakagawara, A.and Sakiyama, S.: "Down-regulation of protein kinase C-alpha and gamma and TPA-induced neurite formationin DAN-transformed neuroblastoma cells." FEBS Lett.440. 25-28 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Wu, Y.-P., Hiwasa, T., Isogai, E., Sonoda, T., Kita, K., Chen, Z., Sugaya, S., Yamamori, H.Tanzawa, H.and Suzuki, N.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line" Int.J.Oncol.13. 1241-1245 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Kikuno, K., Kita, K., Nomura, J., Hiwasa, T., Yonemitsu, H.and Suzuki, N.: "Search for genes responsible for UV susceptibility of human cells : involvemant of syndecan-1 in UV response." Biochem.Biophys.Res.Cummun.253. 519-523 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Hiwasa, T., Arase, Y., Chen, Z., Kita, K., Umezawa, K., Ito, H.and Suzuki, N.: "Stimulation of ultraviolet-induced apoptosis of human fibroblast UV^1-1 cells by tyrosine kinase inhibitors." FEBS Lett.444. 173-176 (1999)
Description
「研究成果報告書概要(欧文)」より
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