| Project/Area Number |
07457488
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
SAKUDA Masayoshi Osaka University, Faculty of Dentistry, Professor, 歯学部, 教授 (00028755)
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| Co-Investigator(Kenkyū-buntansha) |
CHISOKU Hirohisa Osaka University, Dental School Hospital, Resident, 歯学部・附属病院, 医員
KATO Itsuro Osaka University, Dental School Hospital, Resident, 歯学部・附属病院, 医員
OMAE Masatoshi Osaka University, Dental School Hospital, Resident, 歯学部・附属病院, 医員
SUMI Tetsuro Osaka University, Faculty of Dentistry, Assistant Professor, 歯学部, 助手 (40252697)
NAKAZAWA Mitsuhiro Osaka University, Dental School Hospital, Assistant Professor, 歯学部・附属病院, 助手 (70217701)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | EGF receotor / Receptor overexpression / Salivary gland tumor / Tumor growth control / 腫瘍増殖制御 / チロシンキナーゼ阻害剤 |
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| Research Abstract |
We transfected human epidermal growth factor receptor gene into tumorigenic mouse submandibular glamd epitelial cells, and examined their changes in a proliferative capacity after the transfection in comparison with untransfected TMSG cells. Transfected cells (TMSG-EGFR) showed overexpressed hEGFR molecule on their surface. TMSG-EGFR cell proliferation was much faster than that of TMSG cekks and etimulated by EGF and TGF-alpha in dose dependent manner. TMSG-EGFR cells demonstrated a resistance to TGF-beta which strongly inhibited TMSG cell proliferation. TMSG-EGFR cells formed markedly faster and larger tumors in synergic mice than did TMSG cells. Since TMSG-EGFR cells in culture were highly resposive to EGF.Effects of EGFR on TMSG-EGFR tumor growth in vivo was examined. To study this, submandibular glands, which are known to produce more than 95% of EGF in male mice were removed. Plasma EGF levels in sialoadenectomized mice were markedly decreased for 3 to 5 weeks after surgery. TMSG-EGFR tomors shwed prfoundly retarded growth in the sialoadenectomized mice, whereas TMSG tumor growth showed no change. These results suggest that TMSG-EGFR tumor growth was influenced by circulating EGF which was secreted form submandibular glands, TMSG-EGFR tumor growth in culture and in mice was significantly diminished by a tyrosine kinase inhibitor, whereas TMSG growth was not affected by this agent. In xonxlusion, (1) overexpression of EGFR in cancer cells not only increase a responsiveness to EGF but might cause an acquisition of a responsiveness to other growth factors and a resistance to growth inhibitory factors. These changes, at least in part, might account for an increased overall proliferative capacity of cancer cells with aberrant EGFR expression. (2) there might be a possibility that pharmacologic inhibitor of tyrosine kinases are potent anti-cancer agents.
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