C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene define HIF-1alpha protein expression in non-small cell lung cancer.
OBJECTIVE
In this study, we investigated whether polymorphisms of the HIF-1alpha gene may account for the patterns of HIF-1alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1alpha down-stream proteins.


METHODS
Specific HIF-1alpha 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 , 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 , which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1alpha 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-1alpha expression was noted. HIF-1alpha polymorphism did not relate to the expression of the HIF-1alpha downstream proteins analysed, but significant association of HIF-1alpha expression with LDH-5 was confirmed (p=0.008).


CONCLUSIONS
HIF-1alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function.
Koukourakis
Michael I
MI
Department of Radiotherapy/Oncology, Democritus University of Thrace, Medical School, Alexandroupolis, Greece. targ@her.forthnet.gr
Papazoglou
Dimitrios
D
Giatromanolaki
Alexandra
A
Panagopoulos
Ioannis
I
Maltezos
Efstratios
E
Harris
Adrian L
AL
Gatter
Kevin C
KC
Sivridis
Efthimios
E
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D003062:Codon; D003593:Cytoplasm / Q000378:metabolism; D018900:Dinucleotide Repeats; D005091:Exons; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007150:Immunohistochemistry; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D003062:Codon; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit