title: 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.
abstract: 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.
authors.affiliation: Departments of Pathology, Radiotherapy-Oncology, Pneumology and Thoracic Surgery, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzella
authors.forename: Helen
authors.initials: H
authors.lastname: Turley
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.forename: George
authors.initials: G
authors.lastname: Bougioukas
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Gatter
mesh_terms: 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
chemical_list: D051793:Hypoxia-Inducible Factor 1; D012097:Repressor Proteins; D001216:Asparagine; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D011393:Procollagen-Proline Dioxygenase