2002 Fiscal Year Final Research Report Summary
Transcriptional Regulation of Selectin-ligand Synthetase (Fucosyltransferase VII) Related to Ability of Metastasis in Cancer Cells
| Project/Area Number |
13670582
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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 |
Gastroenterology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
HIRAIWA Nozomu Aichi Cancer Center, Molecular Pathology, Senior Associate, 分子病態学部, 主任研究員 (70175553)
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| Co-Investigator(Kenkyū-buntansha) |
KANNAGI Reiji Head, 分子病態学部, 部長 (80161389)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Selectin-ligand / fucosyltransferase VII / Tax / CRE / T-box / one-hybrid / CREB / ATF / T-bet |
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| Research Abstract |
Fucosyltransferase VII (Fuc-T VII) gene encodes a leukocyte/endothelial cell adhesion molecule -ligand sialyl Lewis X synthetase, the expression of which plays important roles in inflammation and even in metastasis of some cancer cells. We have shown that leukemia cells in patients with adult T-cell leukemia strongly express the sialyl Lewis X, the expression level of which significantly correlates with the degree of extravascular infiltration of the leukemic cells, and that the Fuc-T VII gene is transactivated by the HTLV-1 Tax.
We identified the Tax-responsive element (TaxRE) in the promoter of the Fuc-T VII gene, which contains a half-palindromic cAMP-responsive element (CRE). We found that several members of the CREB/ATF family and unidentified factors bind to this TaxRE being much homologous to the Tax-responsive viral CRE in the HTLV-1 long terminal repeat-promoter. In addition to the structural similarity, reporter analysis revealed that the TaxRE also bears functional resemblance to the viral CRE, differing from cellular CREs such as ** the somatostatin gene promoter.
To clarify the mechanism of such fransactivation in the TaxRE, we utilized the yeast one-hybrid system to clone cDNAs encoding TaxRE-binding factors involved in this transactivation. Besides members of CREB/ATF family, one cDNA was identified as the human homologue of one of the transcription factor T box family, T-bet, T-bet reportedly plays a critical role in differentiation of T lymphocyte to Th1. However, the exact binding sequence of T-bet and the mechanism of transactivation remain to be studied. We showed that T-bet actually binds to the 5' part of the TaxRE and also associates with Tax in vivo, and that T-bet is involved in the regulation of the Fuc-T VII gene in association with CREB/ATF family and Tax. These results suggest an important role for T-bet in HTLV-1 Tax-mediated Fuc-T VII gene transactivation.
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Research Products
(14 results)
