Abstract
Abstract We have immortalized human normal proximal bronchial epithelial cells (HBECs) for the study of lung tumors arising in the central compartment of the lung, and now have over 30 of these strains (growing in defined KSFM media) including many isogenic derivatives with various oncogenic changes (Can Res 2004, Can Res 2006). We have extended this by immortalizing normal distal (small airway) epithelial cells that serve as models for the study of tumors arising in the peripheral compartment of the lung. Using Cdk4 and hTERT exogenous expression vectors (as used for HBECs) and serum free defined media, we have immortalized (N= 19) human small airway epithelial cells (HSAECs) from peripheral lung. We have characterized the HBECs and HSAECs and found they have the property of lung basal /stem cells. In the current study, we compared the genome-wide RNA expression profile of HBECs/ HSAECs with 108 lung tumor cell lines and identified a panel of genes that are differentially expressed in these two cell types. We found ∼ 1200 genes that are 2 fold over expressed in tumor cells lines compared with HBECs/HSAECs (p ≤ 0.005). Many known lung tumor oncogenes such as members in cancer/testis (CT) antigen families (XAGE/GAGE/MAGE), proliferation-promoting E2F2 transcription factors, and Kinesin family are over-expressed in tumor lines validating the comparison strategies. In addition, we found genes that had been shown to be involved in other types of tumors but had not been reported in lung tumors. Importantly, we found several genes that had not been implicated as oncogenes previously, thus these are potential novel oncogenes for lung tumor transformation. We also found ∼1300 genes that are 2 fold over expressed in HBECs/HSAECs compared with tumor cell lines (p≤ 0.006). Many of the genes are lung basal cell markers (Keratin and Laminin family members) or known tumor suppressor genes (p53 binding genes and metallothionein genes) as expected. Like in the case of tumor specific genes, we found several genes that had not been reported functioning in the inhibition of tumor transformation. Thus, these are candidate tumor suppressor genes. The current study showed that the immortalized HBEC and HSAECs are ideal models for the discovery of novel oncogenes and tumor suppressor genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2342. doi:1538-7445.AM2012-2342
Published Version
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