The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Abstract

Abbreviations used: ADC -adenocarcinoma; CDK2 -cyclin-dependent kinase 2; cDNAcomplementary DNA; COX-2 -cyclooxygenase 2; C T -cycle threshold; DNAdeoxyribonucleic acid; GAPDH -glyceraldehyde-3-phosphate dehydrogenase; hTERThuman telomerase reverse transcriptase; IHC -immunohistochemistry; LATS2 -homolog of large tumour suppressor 2, Drosophilae; LCC -large cell carcinoma; MDM2 -mouse double minute 2 homolog; mRNA -messenger RNA; NSCLC -non-small cell lung cancer; p21 -cyclin-dependent kinase inhibitor 1A; p53 -tumour protein p53; PCR -polymerase chain reaction; pTNM -pathological tumour-node-metastasis; RB -retinoblastoma; RNAribonucleic acid; r s -Spearman's rank correlation coefficient; RT-PCR -real time PCR; S100A2 -S100 calcium binding protein A2; SCC -squamous cell carcinoma , we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas

“…LATS2 mutations are rare [17,18] but other mechanisms have been reported to cause down-regulation of its expression such as promoter hypermethylation [19] and micro-RNA regulation [20,21]. The relation between reduced LATS2 expression and lung cancer progression, and the underlying mechanisms remain unknown.…”

S100A2 (S100 calcium binding protein A2)

“…High expression of S100A2 is associated with metastasis and predicts survival in early stages of NSCLC. These findings are supported by studies in a mouse model of non-small cell lung cancer (NSCLC) where NOD/SCID mice xenografted with NSCLC cells overexpressing S100A2 demonstrated significantly more metastases than vector alone transfected cells (Heighway et al, 2002;Diederichs et al, 2004;Smith et al, 2004;Wang et al, 2005;Zech et al, 2006;Bartling et al, 2007;Bulk et al, 2009;Strazisar et al, 2009a;Strazisar et al, 2009b).…”

The intrabody targeting of hTERT attenuates the immortality of cancer cells

“…The apoptotic cells were then evaluated by flow cytometry analysis. Since hTERT has been reported to interact with several cell cyclins [37], we performed a cell cycle analysis via PI staining. A significant increase in the content of S-phase cells was observed in AhtscFv-treated cancer cell groups but not in UrscFv-treated cancer cell groups.…”