Expression of apoptosome pathway-related transcripts in non-small cell lung cancer

Abstract

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). 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. 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. 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.