2012 Fiscal Year Final Research Report
Analysis and clinical application of DNMT3L, a novel marker for human embryonal carcinoma
| Project/Area Number |
22390303
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
CHANO Tokuhiro 滋賀医科大学, 医学部, 准教授 (40346028)
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| Co-Investigator(Renkei-kenkyūsha) |
ISONO Takahiro 滋賀医科大学, 実験実習支援センター, 准教授 (20176259)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 腫瘍学 / 精巣腫瘍のエピジェネティックス |
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| Research Abstract |
We have advanced our research by focusing on the two unique biogical features of TGCTs. Most TGCTs are curable even at the metastatic stage since they are extremely sensitive to cisplatin based chemotherapy. However, some NSGCT cases are refractory to any type of chemotherapy. EC is considered a stem cell component of NSGCT. EC cells may acquire resistance to chemotherapy in parallel with differentiation.EC has highly malignant poteintial in nonseminomatous TGCT. Therefore, control of EC is a key to success for patients with nonseminomas or metastatic TGCTs. Through this project, we have shown that DNMT3L, a fetal specific DNA methyltransferase like protein, is a novel marker and essential for the growth of human embryonal carcinoma (Clin Cancer Red 2010).EC has highly malignant poteintial in nonseminomatous TGCT. To further study role of stemness genes in TGCT development, we also have examined effect of SOX2 inhibition in EC cells. The study has shown that the therapeutic potential of SOX2 silencing for EC in vitro and in vivo. Applying SOX2-siRNA may be a novel therapy for NSGCT containing EC cells. To further evaluate epigenetics of TGCTs, we have ezmined methylation patterns of DNA repetitive elements in TGCTs. The results showed that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ betweenTGCTs and cancer cells of somatic tissue origin (Mol Carcinogenesis 2012). Finally we have proposed underlying mechanism to define biological and clinical characteristics of TGCTs in view of epigenetics (Int J Urol 2012).
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