| Project/Area Number |
18K06973
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨髄異形成症候群 / 20番染色体長腕欠失 / 染色体欠失 / がん抑制遺伝子 / 20番染色体長腕 |
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| Outline of Final Research Achievements |
We tried to identify and characterize candidate genes involved in molecular pathogenesis of myelodysplastic syndromes (MDS) development from common deleted lesion of del(20q) which is frequently observed in MDS. We identify two genes, PTPN1 and BCAS4, as candidate genes. Reduced expression of these genes was associated with inferior survival of the patients. We explored biological significance of these genes in myeloid neoplasms, including MDS. Overexpression and knock-down experiments showed that these genes negatively regulate cell growth in myeloid tumor cells. Molecular biological analyses showed that PTPN1 suppresses expression of CyclinD1 and BCL-xL via decreased phosphorylation of tyrosine residues of STAT5, indicating that PTPN1 negatively controls cell growth by its phosphatase activity. Overexpression of BCAS4 results in cell cycle arrest at G1/S, and decreased cell growth on K562 and SKM-1 cell lines.
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄異形成症候群は高齢者に多く、また有効な治療法に乏しい難治性疾患である。本症候群は不均一な疾患であり、分子病態も複雑である。本研究は骨髄異形成症候群で高頻度にみられる20番染色体長腕欠失を手がかりに、疾患関連遺伝子候補を同定し、その臨床的意義を検討した。その結果をもとに、PTPN1とBCAS4の発現低下の臨床的意義を明らかにした。さらに細胞および分子生物学的検討により、これらの遺伝子の発現低下がもたらす生物学的意義を明らかにした。本研究により、本症候群の分子病態の一部が明らかにされたと考える。さらに研究成果が新規治療法開発につながることが期待される。
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