| Project/Area Number |
02454381
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Shinshu University (1991-1992)
Kyoto University (1990) |
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Principal Investigator |
FUJII Shingo Shinshu Univ.,School of Med.,Professor, 医学部, 教授 (30135579)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Ikuo Kyoto Univ.,School of Medicine,Associate Professor, 医学部, 講師 (90192062)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1990: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Cervical Squamous Neoplasia / Human Papillomavirus / Estrogen Receptor / Progesterone Receptor / Epidermal Growth Factor Receptor / C-erbB-2 Protein / ADF / Thioredoxin / Immunogloblin / HPV DNA / replication / Progesterone / EGFR / CーerbBー2 Protein / ADF / thioredoxin / estrogen receptor / progesterone receptor / Kiー67 / human papiuoma virus |
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| Research Abstract |
The analysis of Langerhans cell in the cervical squamous epithelium, and IgG and IgA in the cervical mucus revealed that the cervix possesses a local defense mechanism in the follicular phase of the menstrual cycle. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasel cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk of human papillomavirus (HPV) infection. As factors regulationg growth and differentiation of normal cervical squamous epithelium, sex steroids through the expression of estrogen receptors(ER) and progesterone receptors (PR), epidermal growth factor receptor (EGFR), and C-erbB-2 protein were suggested. Howeve
… More
r, the squamous epithelium infected by HPV showed down-expression of ER and up-expression of PR which were the characteristics of receptor status of normal cervical squamous proliferation. Moreover, transfection of HPV 16 DNA into the ER-positive mammary cancer cell line (ZR-75-1) resulted in its down-expression of ER. This suggested that HPV DNA directly affects the expression of ER. Moreover, up-expression of PR in the HPV-infected squamous neoplasia suggested that, through the glucocorticoid responsive element of HPV, progesterone promotes the proliferation of HPV-infected squamous epithelium. In addition, up-expression of EGFR and down-expression of C-erbB-2protein were observed in the HPV-infected squamous epithelium. Since C-erbB-2 protein expression was closely associated with the differentiation of normal cervical epithelium, these results suggest that HPV-infection affects the differentiation of cervical squamous cells. And co- expression of ADF/thioredoxin and HPV DAN in the neoplastic cervical squamous epithelium suggest that ADF-expression is closely associated with HPV DNA replication. In summary, a human sexual behavior irrespective of the menstrual cycle may be an inherent risk for HPV-infection. HPV infection possibly induces down-expression of ER and up- expression of PR which are the receptor status of squamous proliferation, and up-expression of EGFR and down expression of C-erbB-2 protein, and abnormal ADF-expression. These results suggest that HPV infection is deeply involved in the neoplastic transformation of cervical squamous cells. Less
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