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Molecular insights into the transcri...

Lee, Min Gyu X.

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Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes./
Author:	Lee, Min Gyu X.
Description:	134 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4775.
Contained By:	Dissertation Abstracts International64-10B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3107533
ISBN:	0496550828

Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes.
Lee, Min Gyu X.

Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes. - 134 p.

Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4775.

Thesis (Ph.D.)--The Johns Hopkins University, 2004.

One of the most common biochemical phenotypes of highly malignant, rapidly growing tumors is their ability to utilize glucose at high rates dependent on hexokinase, the first enzyme of the glycolytic pathway. In such tumors, hexokinase is markedly elevated (>100 fold) and plays an essential role in sustaining the high glycolytic phenotype. Among the four mammalian hexokinase types (HK I--IV), type II (HKII) is predominantly overexpressed in such tumors. In contrast, HKII expression is nearly silent in many normal cells, e.g. hepatocytes. Molecular mechanisms involved in the differential regulation of the HKII gene have not been well understood. Using AS-30D hepatoma cells as a highly glycolytic cancer cell model, work described here has shown that the enhanced activity of the HKII promoter resides within a short segment (-281 to -35) of the proximal region and that the transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB interact with sites in this region. In addition, the transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB appear to reside together in a complex bound to the proximal promoter region thereby activating HKII expression. In contrast to hepatoma cells, the levels of transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB are very low in primary hepatocytes and the binding of these factors to the HKII promoter is not detectable under the conditions of the assay employed. In summary, these studies provide novel insights into how the HKII gene may be differentially regulated in normal and cancer cells. Finally, in an independent but related study, it has been shown that the transcription factor Mnt/Rox is induced by a pH decrease in the medium.

ISBN: 0496550828Subjects--Topical Terms:

1017719
Biology, Molecular.

Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes.
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100 1 $a Lee, Min Gyu X. $3 1925968
245 1 0 $a Molecular insights into the transcriptional regulation of the type II hexokinase gene in highly glycolytic hepatoma cells and hepatocytes.
300 $a 134 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4775.
500 $a Adviser: Peter L. Pedersen.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2004.
520 $a One of the most common biochemical phenotypes of highly malignant, rapidly growing tumors is their ability to utilize glucose at high rates dependent on hexokinase, the first enzyme of the glycolytic pathway. In such tumors, hexokinase is markedly elevated (>100 fold) and plays an essential role in sustaining the high glycolytic phenotype. Among the four mammalian hexokinase types (HK I--IV), type II (HKII) is predominantly overexpressed in such tumors. In contrast, HKII expression is nearly silent in many normal cells, e.g. hepatocytes. Molecular mechanisms involved in the differential regulation of the HKII gene have not been well understood. Using AS-30D hepatoma cells as a highly glycolytic cancer cell model, work described here has shown that the enhanced activity of the HKII promoter resides within a short segment (-281 to -35) of the proximal region and that the transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB interact with sites in this region. In addition, the transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB appear to reside together in a complex bound to the proximal promoter region thereby activating HKII expression. In contrast to hepatoma cells, the levels of transcription factors Sp1, Sp2, Sp3, NF-Y, and CREB are very low in primary hepatocytes and the binding of these factors to the HKII promoter is not detectable under the conditions of the assay employed. In summary, these studies provide novel insights into how the HKII gene may be differentially regulated in normal and cancer cells. Finally, in an independent but related study, it has been shown that the transcription factor Mnt/Rox is induced by a pH decrease in the medium.
590 $a School code: 0098.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Biology, Cell. $3 1017686
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0307
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690 $a 0992
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 64-10B.
790 1 0 $a Pedersen, Peter L., $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3107533