Expression of apoptosome pathway-related transcripts in non-small cell lung cancer.
OBJECTIVE
Tumour cells killing by cytotoxic therapies largely depends on triggering the intrinsic apoptosome-mediated caspase activation pathway but it had never been evaluated whether the expression of transcripts encoding the core components of apoptosome pathway is altered in non-small cell lung carcinoma (NSCLC).


METHODS
We investigated the expression status of several apoptosome pathway-related transcripts including Apaf-1, procaspase-9, -3, -6, -7 and Smac in tumour and lung tissue samples from 65 surgically treated NSCLC patients and in 10 NSCLC cell lines with using real time RT-PCR.


RESULTS
NSCLC tissues and cell lines showed significantly increased expression of procaspase-9, -3, -6 and Smac mRNAs as compared to the lungs and expression of these transcripts was simultaneously upregulated in a subset of NSCLCs belonging to different histopathological type, grade and stage categories. The expression of procaspase-7 mRNA in NSCLC tissues and cell lines and lungs was not significantly different. By contrast, the expression of Apaf-1 mRNA was frequently downregulated in the tumours as compared to matched lungs. Nevertheless, the examined NSCLC cell lines showed significantly higher expression of Apaf-1 mRNA than the lungs. The expression of Apaf-1, procaspase-9 and -6 mRNAs was higher in lung adenocarcinomas as compared to squamous cell lung carcinomas but the expression levels of the studied apoptosome pathway-related transcripts in the tumours were independent of tumour's grade and stage.


CONCLUSIONS
The results of the present study suggest that there is a subgroup of NSCLCs, which may be intrinsically primed for apoptosis through upregulated expression of transcripts encoding the apoptosome pathway components.
Krepela
Evzen
E
Clinic of Pneumology and Thoracic Surgery, University Hospital Bulovka and 3rd Faculty of Medicine, Charles University, Budínova 2, 180 81, Prague 8, Czech Republic. krepelae@fnb.cz
Procházka
Jan
J
Fiala
Pavel
P
Zatloukal
Petr
P
Selinger
Pavel
P
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
C506592:APAF1 protein, human; D000199:Actins; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D014408:Biomarkers, Tumor; C412403:DIABLO protein, human; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases