Roles of X chromosomes as cancer susceptibility gene locus.
| Project/Area Number |
15591680
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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 |
Urology
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| Research Institution | Department of Urology, Faculty of Medicine, Shiga University of Medical Science |
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Principal Investigator |
OKADA Yusaku Shiga University of Medical Science, Department of Urology, Professor, 医学部, 教授 (20127062)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Keisei Shiga University of Medical Science, Department of Urology, Research Assistant, 医学部, 助手 (50303780)
杉原 洋行 滋賀医科大学, 医学部, 助教授 (30171169)
川上 亨弘 滋賀医科大学, 医学部, 助手 (90346023)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | X chromosome / inactivation / XIST / Klinefelter syndrome / oncogene / breast cancer / ovarian cancer / 癌感受性遺伝子 |
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| Research Abstract |
Barr body loss in female derived canccer cells (eg, breast cancer or ovarian cancer) has been reported in 1970's. Barr body loss in cancer has been recognized as an indicator of poor prognosis. However mechanism for barr body loss remain unknown. Klinefelter syndrome is a sex chromosome abnormality with a prevalence of 1/500 in males. Patients with Klinefelter syndrome (47XXY) have an increased risk of developing several types of cancer, such as breast cancer and extragonadal germ cell tumors. The increased risk of several types of cancer in Klinefelter syndrome (47XXY) suggests that the extra X chromosome may be involved in the tumorigenesis associated with this syndrome.
Here, we show that cancer cells (PSK-1) derived from a patient with Klinefelter syndrome (47XXY) showing loss of an inactive X chromosome subsequently gained active X chromosomes. Furthermore we extended the characterization of loss-of-inactive X in a series of 22 female-derived cancer cell lines (8 breast cancer cell lines, 7 ovarian cancer cell lines, and 7 cervical cancer cell lines). The data demonstrate that loss-of-inactive X in the female-derived cancer cells is mainly achieved by loss of an inactive X chromosomes followed by multiplication of an identical active X chromosomes. However, distinctive pathways, including reactivation of an inactive X chromosome, are also involved in the mechanisms for loss-of-inactive X and gain-of-active X in female derived cancer cells.
The loss-of-inactive X followed by gain-of-active X found in the present study signifies disruption of the dosage compensation. This phenomenon may imply oncogenic, rather than tumor suppressor, roles of X chromosomes in Klinefelter syndrome and female-derived cancer cells.
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Report
(3 results)
Research Products
(12 results)
