1999 Fiscal Year Final Research Report Summary
Expression cloning of sialyltransferase involved in malignant progression of human RCC
Project/Area Number |
09470338
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
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Research Institution | Tohoku University |
Principal Investigator |
SAITO Seiichi Tohoku Univ.Hospital, Research Associate, 医学部附属病院, 助手 (80235043)
|
Co-Investigator(Kenkyū-buntansha) |
SATO Makoto Tohoku Univ.Graduate school of Medicine, Research Associate, 大学院医学系研究科, 助手 (70282134)
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Project Period (FY) |
1997 – 1999
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Keywords | renal cell carcinoma / sialyltransterase / malignant progression / differentiation / globo-series ganglioside |
Research Abstract |
In all attempt to identify α 2, 3-sialyltransferase involved in synthesis of monosialosyl galactosyl globoside (MSGG), the first substance of globo-series ganglioside, associated with the malignant progression of human renal cell carcinoma (RCC), we utilized both expression cloning procedure and PCR method. Thus far, we could not obtain α 2, 3-sialyltransferase by expression cloning procedure, but 5' precursor of rRNA, placental transforming growth factor β, unknown cDNA, etc. were identified as concentrated cDNA by this procedure. We are now investigating the relationship between these cDNA and expression of MSGG.We obtained hST3Gal I and hST3Gal IV by PCR method. By Northern analysis, there was no clear correlation between hST3Gal I and the malignant progression of human RCC.None of the stable transfectants with hST3Gal I examined showed expression of MSGG.Stable transfectant with hST3Gal IV showed moderate increase of MSGG.However, hST3Gal IV transcript increased prominently in almost all normal renal tissues and decreased in most cases of cancer tissues. It was suggested that hST3Gal IV is associated with renal differentiation. From these results, it was anticipated that there is another a 2, 3-sialyltransferase determining the sysnthesis of MSGG.Investigation of this putative sialyltransferase is still underway. During this research, we identified N-acetyl-galactosaminyl disialosyl typel chain paragloboside (GalNAc DSPG-1) as a novel ganglioside, and found that DSGG is distributed in cells of mesoderm origin. We also found that expression of MSGG is inversely related to that of GM3 in human RCC.
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