1999 Fiscal Year Final Research Report Summary
Induction of apoptosis in gynecologic cancer cells by the soluble IGF-I receptor.
| Project/Area Number |
10671544
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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 |
HONGO Atsushi Medical Hospital, Okayama University assistant, 医学部・附属病院, 助手 (10301293)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHINOUCHI Mitsuo Medical Hospital, Okayama University assistant professor, 医学部・附属病院, 講師 (50261235)
MIYAGI Yasunari Medical Hospital, Okayama University assistant, 医学部・附属病院, 助手 (10273989)
KODAMA Junichi Medical Hospital, Okayama University assistant, 医学部・附属病院, 助手 (90263582)
KUDO Takafumi Medical School, Okayama University professor, 医学部, 教授 (90127556)
OKUDA Hiroyuki Medical School, Okayama University professor, 医学部, 教授 (30033286)
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| Project Period (FY) |
1998 – 1999
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| Keywords | IGF-I receptor / IGF-I / transformation / tumorigenicity / apoptosis / chemosensitivity / bystander effect |
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| Research Abstract |
1) In order to evaluate the anti-tumor effect of the IGF-I receptor blockage in gynecologic malignancies, We transfected an antisense mRNA expression vector into human cervical cancer derived cell lines, SiHa, HeLa S3, and C33A and established stable transformants. Introduction of the antisense slightly inhibited growth in mono-layer and makedly inhibited anchorage-independent growth in soft agar and tumorigenicity in nude mice. These results were presented at the 90th annual meeting of AACR (Philadelphia PA, USA) and published in Cancer Research.
2) Then we tried to use the soluble IGF-I receptor with a bystander effect that would be an advantage in clinical applications. We stably transfected the soluble IGF-I receptor in human ovarian carcinoma derived cell line CaOV-3. The soluble receptor was detected as a 70kDa protein from total cell lysates as well as conditioned media. Anchorage-independent growth of the soluble IGF-I receptor clones was strongly inhibited and conditioned media from transfected clones showed bystander effects. Tumorigenicity in nude mice was abrogated in transfected clones and co-culture of the parental cells with transfected clones showed bystander effects in vivo. Chemosensitivity against paclitaxel was tested by clonogenic assay and transfected clones showed much higher sensitivities. Percentages of the apoptotic cells after paclitaxel treatment were significantly higher in transfected clones ; indicating the abrogation of the anti-apoptotic activity of the IGF-I receptor caused this effect. These results were presented at the 5th International Symposium on IGFs (Brighton, UK), the 92nd annual meeting of AACR (New Orleans LA, USA) and submitted for publication
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