Expression of prolyl-hydroxylases PHD-1, 2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activated HIF pathway.
The oxygen sensitive prolyl-hydroxylase domain enzymes (PHDs) and the asparagines hydroxylase (FIH, factor inhibiting HIF) regulate the transcriptional activity of HIFs. We assessed the expression of these enzymes in a series of 73 non-small cell lung carcinomas (NSCLC). A direct association of PHDs with FIH and of the PHDs/FIH with HIFs expression was noted. Thirty three of 73 cases had high HIF/PHD expression, predicting intense HIF activity; 19/73 cases had low HIF and high PHD expression mimicking the normal bronchial pattern; and 18/73 cases had low HIF/PHD (inactive HIF pathway). High lactate dehydrogenase LDH5 expression was noted in cases with high HIF/PHD phenotype. The value of such a classification in defining different metabolic phenotypes of NSCLC deserves further evaluation.
Giatromanolaki
Alexandra
A
Departments of Pathology, Radiotherapy-Oncology, Pneumology and Thoracic Surgery, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Koukourakis
Michael I
MI
Pezzella
Francesco
F
Turley
Helen
H
Sivridis
Efthimios
E
Bouros
Demosthenes
D
Bougioukas
George
G
Harris
Adrian L
AL
Gatter
Kevin C
KC
D001216:Asparagine / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation
D051793:Hypoxia-Inducible Factor 1; D012097:Repressor Proteins; D001216:Asparagine; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D011393:Procollagen-Proline Dioxygenase