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C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1 alpha gene define HIF-1 alpha protein expression in non-small cell lung cancer

Koukourakis, Michael I. ; Papazoglou, Dimitrios ; Giatromanolaki, Alexandra ; Panagopoulos, Ioannis LU ; Maltezos, Efstratios ; Harris, Adrian L. ; Gatter, Kevin C. and Sivridis, Efthimios (2006) In Lung Cancer 53(3). p.257-262
Abstract
Objectives: In this study, we investigated whether polymorphisms of the HIF-1 alpha gene may account for the patterns of HIF-1 alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1 alpha down-stream proteins. Methods: Specific HIF-1 alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number NM_001530, which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number NM_001530, which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13.... (More)
Objectives: In this study, we investigated whether polymorphisms of the HIF-1 alpha gene may account for the patterns of HIF-1 alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1 alpha down-stream proteins. Methods: Specific HIF-1 alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number NM_001530, which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number NM_001530, which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1 alpha and down-stream proteins (VEGF, LDH-5, GLUT-1) was also performed in tumor material. Results: A strong association of the P582S polymorphism and of GT repeat polymorphism higher than 14/14 with increased HIF-1 alpha expression was noted. HIF-1 alpha polymorphism did not relate to the expression of the HIF-1 alpha downstream proteins analysed, but significant association of HIF-1 alpha expression with LDH-5 was confirmed (p=0.008). Conclusions: HIF-1 alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function. (C) 2006 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
expression, HIF-1 alpha gene, polymorphism, lung cancer
in
Lung Cancer
volume
53
issue
3
pages
257 - 262
publisher
Elsevier
external identifiers
  • wos:000240422500001
  • scopus:33747061025
  • pmid:16837101
ISSN
1872-8332
DOI
10.1016/j.lungcan.2006.05.025
language
English
LU publication?
yes
id
64888835-c2ef-4918-b3c7-aed0a4c11782 (old id 394696)
date added to LUP
2016-04-01 12:15:36
date last changed
2021-04-13 02:48:21
@article{64888835-c2ef-4918-b3c7-aed0a4c11782,
  abstract     = {Objectives: In this study, we investigated whether polymorphisms of the HIF-1 alpha gene may account for the patterns of HIF-1 alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1 alpha down-stream proteins. Methods: Specific HIF-1 alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number NM_001530, which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number NM_001530, which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1 alpha and down-stream proteins (VEGF, LDH-5, GLUT-1) was also performed in tumor material. Results: A strong association of the P582S polymorphism and of GT repeat polymorphism higher than 14/14 with increased HIF-1 alpha expression was noted. HIF-1 alpha polymorphism did not relate to the expression of the HIF-1 alpha downstream proteins analysed, but significant association of HIF-1 alpha expression with LDH-5 was confirmed (p=0.008). Conclusions: HIF-1 alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function. (C) 2006 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Koukourakis, Michael I. and Papazoglou, Dimitrios and Giatromanolaki, Alexandra and Panagopoulos, Ioannis and Maltezos, Efstratios and Harris, Adrian L. and Gatter, Kevin C. and Sivridis, Efthimios},
  issn         = {1872-8332},
  language     = {eng},
  number       = {3},
  pages        = {257--262},
  publisher    = {Elsevier},
  series       = {Lung Cancer},
  title        = {C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1 alpha gene define HIF-1 alpha protein expression in non-small cell lung cancer},
  url          = {http://dx.doi.org/10.1016/j.lungcan.2006.05.025},
  doi          = {10.1016/j.lungcan.2006.05.025},
  volume       = {53},
  year         = {2006},
}