Abstract 5219: Molecular phenotype of an epithelial-like subset of the NCI-60 human tumor cell lines and relevance to gene expression patterns in TCGA normal breast and breast cancer tissue samples.

Abstract

Abstract Better cancer therapy is likely to come from molecular characterization of individual patients’ tumors that will permit selection and development of tailored therapies. To that end, many bioinformatic studies have been carried out on human tumor cell lines and tissue samples. Large gene expression databases have become available for the National Cancer institute's 60 human tumor cell lines (NCI-60) and for normal breast and breast cancer tissue samples from the Cancer Genome Atlas (TCGA) Research Network. We aimed to infer functional relationships among expression-correlated genes based on these data and on published information about molecular interactions. In addition, we asked how or to what extent inferences based on cell line data may apply to human tissue samples. Among the best-defined cell phenotypes are those of epithelia. Epithelial cells have polarity that distinguishes an apical region, directed towards a surface or lumen, from a basolateral region resting on a connective tissue basement membrane. Polarity is created by transport of appropriate molecular components as cargo in vesicles that are moved by motor proteins along cytoskeletal tracks to the relevant cell regions. Epithelial polarity is maintained by molecular structures, such as tight junctions, that prevent back-flow between the apical and basolateral surfaces of the cell. We initially defined an epithelial-like phenotype on the basis of expression of genes coding for tight junction and adherence junction proteins and their family members. Among the NCI-60, we found 11 cell lines that express a mutually correlated subset of those genes. The relevant cell lines were breast cancer MCF7 and T47D; colon cancer COLO205, HCC_2998, HCT_116, HCT_15, HT29, and KM12; lung cancer NCI_H322M; and ovary cancer OVCAR_3 and OVCAR_4; we call these the NCI-60 epithelial consensus (NEC) cell lines. The following tight junction genes were selectively expressed in the NEC cell lines: TJP3, CLDN3, CLDN4, CLDN7, OCLN, MARVELD2, and MARVELD3. Highly correlated with these genes was the adherence junction gene CDH1/E-cadherin (as expected). We then assembled an expanded list of 75 genes that were selectively expressed in the NEC cell lines, and found that many of them function in the epithelia-specific processes summarized above. With some notable exceptions, the tight junction and adherence junction genes co-expressed in the NEC cell lines were also co-expressed in the normal breast and breast cancer tissue samples. An unexpected finding was that some of the normal breast tissue samples expressed a different set of tight junction family genes. This work delineates similarities and differences between epithelial-like NCI-60 cell lines and TCGA breast tissue samples in regard to the expression of functionally defined genes. Citation Format: Kurt W. Kohn, Barry R. Zeeberg, William C. Reinhold, Ari Kahn, Yves Pommier. Molecular phenotype of an epithelial-like subset of the NCI-60 human tumor cell lines and relevance to gene expression patterns in TCGA normal breast and breast cancer tissue samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5219. doi:10.1158/1538-7445.AM2013-5219