Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer

Purpose: Apoptotic cell death contributes to the regulation of tumour regression but can be prevented by proteins of the IAP family. Although survivin can be identified as tumour-specific gene product, the role of other members of the IAP family is mainly unclear in non-small cell lung cancer (NSCLC). Therefore, we hypothesise that hIAP-1, hIAP-2, and XIAP are associated with lung carcinogenesis, too. Methods: To define IAP expression levels, lung tumour samples from 34 NSCLC patients with adenocarcinoma (16) and squamous cell carcinoma (18) were included. Analyses were performed by standardised RT-PCR and immunoblotting, Paired non-tumour lung tissues served as controls. All tumour samples showed a strong survivin mRNA up-regulation compared with non-tumour controls. Results: Investigations of the XIAP mRNA expression revealed an overall increase in lung carcinoma (median: 1,083 vs 605 rel. U; P = 0.02). In contrast, hIAP-2 mRNA was nearly identical in all tumour and control samples. Furthermore, we identified an elevated hIAP-1 mRNA expression especially in patients with adenocarcinoma (median: 8.58 vs 3.44 rel. U; F < 0.01). Using the median increase of 50% determined in all tumours as a cut-off point, 11/16 patients with adenocarcinoma but only 6/18 with squamous cell carcinoma showed an elevation in hIAP-1 mRNA. This hIAP-1 up-regulation could be mainly observed in low, TMN adenocarcinomas (7/9 in TMN 1, median increase: + 289% vs 2/5 in TMN III-IV, + 44.6%). An enhanced mRNA expression of hIAP-1 and XIAP in respective tumours could be confirmed on protein level by immunoblot analyses. Conclusions: Our results indicate an involvement of the anti-apoptotic XIAP in pathogenesis of NSCLC. while hIAP-1 preferentially seems to play an important role in low-stage adenocarcinoma.