The roles of sialyltransferases involved in malignant progression of renal cell carcinoma
| Project/Area Number |
15390483
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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 | Tohoku University |
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Principal Investigator |
SAITO Seiichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80235043)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Makoto Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70282134)
伊藤 明宏 東北大学, 医学部附属病院, 助手 (70344661)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Silayltransferase / renal cell carcinoma / RM2 antigen / prostate cancer / 腎細胞癌 / sialyltransferase / SSEA-4 / ST3 Gal II / siRNA / ACHN / stage-specific embryonic antigen-4 / ST3Gal II / 精巣腫瘍 |
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| Research Abstract |
We have found that ST3Gal II is a stage-specific embryonic antigen-4 (SSEA-4 or MSGb5) synthase, which transfers sialic acid to Gb5. Levels of ST3Gal II mRNA were increased in 7 out of 8 renal cell carcinoma cell lines and all 6 renal cell carcinoma tissues examined using Northern bot analysis. We further tested and found that levels of ST3Gal II were increased in most of 27 cases of renal cell carcinoma using quantitative PCR. From these studies it was indicated that ST3Gal II is associated with carcinogenesis of kidney. Inhibition of ST3Gal II mRNA expression by siRNA was 30% of that by disordered (mock) siRNA using ACHN cell line. Expression of MSGb5 was also decreased by siRNA. Concomitant with suppression of ST3Gal II, proliferation and invasion of ACHN cells were also decreased.
We recently found a novel disialoganglioside, RM2 antigen (β1, 4-GalNAc-disialyl-Lc4) from renal cell carcinoma. We examined expression of RM2 antigen in fresh-frozen sections of 114 cases of renal cell ca
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rcinoma. RM2 antigen was positive in 15 cases (13%), out of which 9 had metastasis already at initial diagnosis and 2 developed metastasis during follow-up period. Since metastasis was detected in 73% (11/15) of RM2 antigen-positive cases, RM2 antigen may have relevance to malignant potential of renal cell carcinoma. RM2 antigen is a unique oligosaccharide composed of lacto-series type I chain and ganglio-series structure. Lacto-series structures were widely distributed in epithelial cells, whereas ganglio-series antigens were prevalent in cells of neuroectodermal origin. On the other hand, whereas prostate cancer develops form epithelium and expresses epithelial characteristics such as prostatic acid phosphatase and PSA, neuroendocrine differentiation is a feature of prostate cancer. Based on these facts, structural characteristics of RM2 antigen may reflect the dual nature of prostate cancer. Thus, we examined expression of RM2 antigen in 75 cases of radical prostatectomy specimens. A clear difference of RM2 expression level was observed between Gleason patterns 3 and 【greater than or equal】4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern 4, high Gleason score, larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure free survival was significantly lower in the higher expression group.
Our study on sialyltransferase and oligosaccharide showed the possibility of treating cancer, which has qualitative or quantitative changes of sugar chain as a general phenomenon, by restoring the level of glycosyltransferase such as sialyltransferase to normal. Less
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Report
(4 results)
Research Products
(17 results)
