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Transcriptional Gene Expression Profiling of Small Cell Lung Cancer Cells ¹

Department of Radiation Biology, The Finsen Centre [N. P., S. M., M. W. P., S. B. S., H. S. P.] and Institute for Inflammation Research, IIR 7521 [K. R., L. F. B.], National University Hospital, Copenhagen DK-2100, Denmark

A global gene expression analysis using oligonucleotide microarrays was performed on many human small cell lung cancer (SCLC) cell lines in cell culture and/or as xenografts. The expression was compared with the expression profiles of 18 normal tissues.

In a hierarchical cluster analysis the cell lines clustered distinctly from normal tissues and grouped into four clusters. One cluster consisted of two related cell lines and was markedly different from the other SCLC cell lines, whereas the rest of the clusters grouped together. Two subclusters contained the classical SCLC types and one subcluster the variant SCLC type, thus identifying many genes with differential expression between the two variants of SCLC. All of the xenografts clustered closest to the cell lines from which they originated and had the same expression levels as the cells grown in culture for the majority of genes.

The analysis confirmed the high expression of many genes identified previously as highly expressed in SCLC cells including neuroendocrine markers, oncogenes, and genes involved in cell proliferation and division. The analysis furthermore identified a number of molecules not identified previously as expressed in SCLC. Several of these are expressed in low or undetectable amounts in the majority of normal tissues and, therefore, are potential targets for new therapeutic approaches. By including the published array profiles of six ressected SCLC tumors from Bhattacharjee et al. (A. Bhattacharjee et al., Proc. Natl. Acad. Sci. USA, 98: 13790–13795, 2001.), the analysis revealed that most of the novel potential targets expressed by SCLC cell lines and xenografts were also expressed in the tumors.

This analysis demonstrates the value of using cell lines and xenografts for expression profiling, when a limited quantity of tumor material is available.

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