| Co-Investigator(Kenkyū-buntansha) |
MESE Hiroshi Okayama University, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, INSTRUCTOR, 大学院・医歯学総合研究科, 助手 (40325098)
SASKI Akira Okayama University, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (00170663)
大山 和彦 岡山大学, 歯学部, 助手 (20169080)
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| Budget Amount *help |
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Doc-1 gene (deleted in oral cancer) is a putative tumor suppressor gene isolated and identified from hamster (HCPC cell line), mouse and human oral keratinocytes. In the present study, we examined whether the doc-1gene could be used as a target gene of gene therapy for oral cancer.
Immunohitochemical analysis for tissues of oral cancer patients: Although Doc-1 protein expression was observed in normal oral mucosa of all cases, the 40% of cases of oral squamous cell carcinomas (OSCC) showed negative staining of Doc-1 protein. In cancer tissues, the staining of Doc-1 protein showed various patterns. There was no statistical correlation between the expression of Doc-1 and some clinico-pathological factors, such as tumor differentiation, mode of invasion, nuclear differentiation and inflammatory cell response. However, the expression of Doc-1 protein was observed in the invasive tumors, the deletion of Doc-1 protein was observed in the noninvasive tumors.
Subcutaneous implantation of the tra
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nsfectant (HCPC (doc)) of hamster OSCC cell line, HCPC-1, without doc-1 expression, which was transfected with doc-1 gene, to nude mice was performed. The tumor volume and weight of mice implanted with HCPC (doc) were bigger than that of mice implanted with HCPC (original). Moreover, HCPC (doc-1) invaded the peripheral muscle, and metastasized to liver and intestine membrane.
It was reported that the expression of Doc-1 protein in various OSCC cell lines was not observed. However, the most of OSCC cell lines of our laboratory expressed Doc-1 protein in western blotting. Only.HSC-3 cell line showed the deletion of Doc-1 protein.
The direct injection of the Doc-1 fusion protein (TAT-HA-doc-1), which was excellent delivery system into mammalian tissues, into the tumor of mice implanted with HSC-3, did not affect the tumor volume and morphology of tumors compared with the control group.
These results suggested that doc-1 gene could not be used as a target gene of gene therapy for oral cancer. And it seems that doc-1 gene may play an important role on the invasion and metastasis rather than tumor suppressor gene. Less
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