2006 Fiscal Year Final Research Report Summary
The Induction of Decsity-Deoendent Inhibition of Cell Growth in Malignant Mesothelioma Cells by the Extracellular Domain of erbB2 for Reduction of Growth of Mesothelioma
| Project/Area Number |
17590790
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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 |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
KUMAGAI Toru Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (80346212)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Mitsuhiro Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90359844)
KIJIMA Takashi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90372614)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Malignant Mesothelioma / Density-dependent Inhibition of Cell Growth / EGFR / The Extracellular Domain of erbB2 / p21 |
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| Research Abstract |
EGFR is involved in the density-dependent inhibition of cell growth, while co-expression of EGFR with erbB2 can render normal cells transformed. In this study, we have examined the effect of a species of p185 that contains the transmembrane domain and the extracellular domain of p185c-neu, on growth properties of a human malignant mesothelioma cell line that co-expresses EGFR and erbB2. The ectodomain form of p185c-neu enhanced density-dependent inhibition of cell growth that was confirmed by trypane blue exclusion tests, morphorogical examination, and cell cycle analysis. We also found that p21 induction appeared to be responsible for this inhibitory effect. Previously the extracellular domain species was shown to suppress the transforming abilities of EGFR and p185c-neu/erbB2 in a dominant-negative manner. The ability of this subdomain to affect tumor growth is significant, as it reduced in vivo tumor growth. Unexpectedly, we found that the domain did not abrogate all of EGFR-functions. We noted that EGFR-induced density-dependent inhibition of cell growth was retained. Tyrosine kinase inhibitors of EGFR did not cause density-dependent inhibition of cell growth of malignant mesothelioma cells. Therefore simultaneously inhibiting the malignant phenotype and inducing density-dependent inhibition of cell growth in malignant mesothelioma cells by the extracellular domain of p185c-neu may represent an important therapeutic advance.
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