Abstract 3921: Amplification of the TFAP2B gene and upregulation of its gene products promote human bronchial epithelial cell (HBEC) transformation and carcinogenesis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.3921-3921
• Main Authors: Wismach, Marnie, Xu, Kai, Chen, Ying, Katz, Ruth, Girard, Luc, Minna, John D., Roth, Jack A., Ji, Lin
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-3921

We previously showed that the transcription factor AP2B (TFAP2B) protein could specifically bind to the promoter of human telomerase reverse transcriptase (hTERT) and selectively activate hTERT in lung cancer cells but not in normal cells. The common 5p15.33 and 6p21.33 chromosomal variants that harbor the hTERT and TFAP2B genes, have been identified as susceptibility loci for lung cancer and show a significant autosomal copy number gain in lung adenocarcinoma. We tested the hypothesis that amplification of the TFAP2B gene and up-regulation of its gene products can transform lung cells and promote tumorigenesis. We first analyzed levels of TFAP2B gene expression in human lung cancer cell lines, small-airway epithelial cells (SAECs),primary normal HBEC and in immortalized or transformed HBECs by gene expression profiling on gene microarrays. Levels of TFAP2B gene expression varied significantly between different cell lines but on average were greater than those of primary normal HBECs and SAECs. A linkage distance cluster analysis of the TFAP2B pathway-associated genes showed a significant classification of lung cancer cell types, distinguishing tumor cells from normal ones. Differential expression of the TFAP2B gene in normal lung and cancer cells was confirmed by qRT-PCR. We analyzed copy number variations (CNVs) specifically linked to hTERT and TFAP2B loci by mining the published genome-wide SNP data set from 370 NSCLC tumor samples and confirmed a significant copy number gain for both hTERT and TFAP2B with average copy numbers of 4.5 and 3.5, respectively. We performed immunohistochemical (IHC) analysis of TFAP2B protein expression in 30 paired human lung tumors and normal lung tissues that are immediately (