Expression analysis of Akt and MAPK signaling pathways in lung tissue of patients with idiopathic pulmonary fibrosis (IPF).
OBJECTIVE
Several studies in patients with lung cancer have shown that epidermal growth factor receptor regulates various tumorigenic processes through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin and Ras/Raf/Mek/Erk (mitogen-activated protein kinase (MAPK)) signalling pathways. The aim of our study is to evaluate whether these pathways are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and to seek indirect evidence of a common pathogenetic pathway with lung cancer. m-RNA expression of oncogenes participating in these two signaling pathways, as well as the combined m-RNA expression of the suppressor genes R-kip and p53 in lung tissue of patients with IPF were evaluated.


METHODS
The study population was composed by two distinct groups. Patients with IPF (n = 25) and control subjects who underwent thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned oncogenes and suppressor genes was performed using real-time reverse transcription polymerase chain reaction.


RESULTS
We found no difference in the overall m- RNA expression between controls and IPF in both investigated pathways. However, Braf has been overexpressed in IPF samples (P = 0.01) in contrast with K-ras that has been found downregulated (P < 0.001) in comparison with controls.


CONCLUSIONS
These findings cannot exclude the hypothesis of involvement of Akt and MAPK signalling pathways in pathogenesis of IPF. However, further investigation is needed in order to verify these data.
Department of Thoracic Medicine, Interstitial Lung Disease Unit, Medical School, University of Crete, Heraklion, Crete, Greece. katerinaantoniou@yahoo.gr
Katerina M
KM
Antoniou
George A
GA
Margaritopoulos
Giannoula
G
Soufla
Emmanouil
E
Symvoulakis
Evi
E
Vassalou
Rena
R
Lymbouridou
Katerina D
KD
Samara
Dimitra
D
Kappou
Demetrios A
DA
Spandidos
Nikolaos M
NM
Siafakas
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D013147:Spirometry; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins