1995 Fiscal Year Final Research Report Summary
Molecular analysis of flg and its products for targeted therapy on brain tumors
| Project/Area Number |
06671373
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TSUBOI Koji Univ.of Tsukuba, Institute of clinical medicine, assistant professor, 臨床医学系, 講師 (90188615)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHII Yoshihiko Univ.of Tsukuba, Institute of clinical med., associate professor, 臨床医学系, 助教授 (50110507)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Glioma / flg / anti-sense / Northern / Southern |
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| Research Abstract |
It has been reported that basic fibroblast growth factor (bFGF) plays an important role in the growth of glioma cells. The gene encoding receptor of bFGF,namely fms-like gene (flg), was analyzed in this study not only to clarify its biological activity in the growth of glioma cells but also to examine its potential to be a molecular target in treatment of malignant gliomas. First we analyzed expression of flg mRNA in brain tumor tissues obtained at surgery using RT-PCR technique. Sixty-five samples were studied, and it was indicated that expression of flg mRNA in glioma tissues were more enhanced than normal brain tissues. Moreover, it's expression was further enhanced in cases with malignant transformation or recurrence. Histopathologically, enchanced flg expression was in correlation with high cellularity in glioma tissues. Based on these facts, we made more detailed molecular analyzes by Southern and Northern blot techniques on cultured glioblastoma cell lines. flg gene amplification was not observed in Southern analysis, while its expression was increased in Northern, indicating its expression should be controlled by upstream unknown transcription factors. In addition, immunohistochemical analyzes indicated that the flg-product was detected more in glioblastoma cell lines than normal fibroblasts. Anti-sense oligo nucleotide effectively suppressed the growth of glioblastoma cells at concentration of 20 muM.All these results indicate that autocrine or paracrine loops of FGF-flg system is essential in glioma cell proliferation, which also indicates that flg can be a good candidate as a molecular target in treatment of gliomas.
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