Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer.
OBJECTIVE
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.
Hofmann
Hans-Stefan
HS
Cardio-Thoracic Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 60120 Halle/Saale, Germany.
Simm
Andreas
A
Hammer
Andreas
A
Silber
Rolf-Edgar
RE
Bartling
Babett
B
D017209:Apoptosis; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D011379:Prognosis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human