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
Giatromanolaki A., Koukourakis MI., Pezzella F., Turley H., Sivridis E., Bouros D., Bougioukas G., Harris AL., Gatter KC.
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.