1998 Fiscal Year Final Research Report Summary
FUNDAMENTAL RESEARCH OF GENE THERAPY FOR CERVICAL CANCER BY ANTISENSE STRATEGY TARGETING IGF-1 RECEPTOR
| Project/Area Number |
09671684
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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 |
Obstetrics and gynecology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
OKUDA Mitsuo OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (50261235)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Junichi OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (90263582)
KAMIMURA Shigehito OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (90281154)
OKUDA Hiroyuki OKAYAMA UNIVERSITY MEDICAL SCHOOL ASSOCIATE PROFESSOR, 医学部, 助教授 (30033286)
HONGO Atsusi OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (10301293)
MIYAGI Yasunari OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (10273989)
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| Project Period (FY) |
1997 – 1998
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| Keywords | IGF-1 / antisense / cervical cancer / HPV |
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| Research Abstract |
The Insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype, and interference with the IGF-IR pathway by antisense or dominant negative mutants causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected IGF-IR antisense mRNA expression plasmid into human papillomavirus (HPV) negative C33a cell line, HPV-16 positive SiHa cell line, and HPV-18 positive HeLa S3 cell line to determine whether the IGF-IR could be a target for cervical cancer cells especially in the presence of HPV. Approximately 30-80% downregulation of IGF-IR expression was observed by western blot in antisense transfected clones. There was a little inhibition in monolayer growth in all cell lines. In C33a cells, wild type and sense clones formed 92-146 colonies in soft agar after 3 weeks, antisense clones formed less than 12 colonies. In SiHa cells, wild type and sense clones formed about 60 colonies after 5 weeks, antisense clones formed 0-3 colonies. In HeLa S3 cells, wild type and sense clones formed 218-291 colonies in soft agar after 2 weeks, antisense clones formed 14-160 colonies. There was a good correlation between IGF-IR downreguration level and inhibition of transformation in soft agar. Tumorigenesis in nude mice was strongly inhibited in HeLa S3 and SiHa clones transfected with the antisense. These results indicate that downregulation of IGF-IR by antisense RNA can reverse the transformed phenotype of human cervical cancer cells even when harboring malignant type HPVs.
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