COMPARATIVE STUDY
JOURNAL ARTICLE
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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; P <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 I, 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.

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