EXPERIMENTAL STUDY OF GENE THERAPY FOR ORAL CANCER USING A TUMOR SUPPRESSOR GENE DOC-1.

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11557160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Surgical dentistry
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: MATSUMURA Tomohiro Okayama University, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, PROFESSOR, 大学院・医歯学総合研究科, 教授 (00028747)
• 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)
• Project Period (FY): 1999 – 2001
• Keywords: oral cancer / oral squamous cell carsinoma / gene therapy / doc-1 / efficacy / tumor suppressor gene / invasion / metastasis

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 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.