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Identification of genes whose expression is upregulated in lung adenocarcinoma cells in comparison with type II alveolar cells and bronchiolar epithelial cells in vivo

Oncogene volume 23, pages 3089–3096 (2004)Cite this article

Abstract

To identify genes whose expression is upregulated in lung adenocarcinoma (AdC) cells in comparison with noncancerous peripheral lung epithelial cells, type II alveolar cells and bronchiolar epithelial cells, as well as AdC cells, were isolated by laser capture microdissection, and subjected to cDNA microarray analysis of 637 human cancer-related genes. Each of the component cells was obtained from several different individuals and analysed independently. As a comparison, two lung AdC cell lines and two primarily cultured normal lung epithelial cell lines were also subjected to cDNA microarray analysis. Four genes, TOP2A, MMP15, MX2 and KOC1, were commonly upregulated in microdissected AdC cells in comparison with microdissected epithelial cells. Hierarchical clustering analysis revealed that differences in gene-expression profiles were more evident between cultured and uncultured cells than between cancerous and noncancerous cells. To further identify the common molecular targets of AdC cells in vivo, quantitative real-time RT–PCR was performed against the four genes upregulated by cDNA microarray analysis. The TOP2A, MMP15, MX2 and KOC1 genes were overexpressed in 10/10 (100%), 8/10 (80%), 5/10 (50%) and 3/10 (30%) microdissected AdC cell samples, respectively, in comparison with any of nine independently microdissected noncancerous epithelial cell samples. The TOP2A gene was commonly overexpressed in lung AdC cells, as previously reported. In addition, the MMP15 and MX2 genes were identified, for the first time, as being commonly overexpressed in lung AdC cells. These results strongly indicate that the MMP15 and MX2 genes could be novel markers for molecular diagnosis and therapy of lung AdC.

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Abbreviations

AdC:

adenocarcinoma

QRT–PCR:

quantitative real-time RT–PCR

LCM:

laser capture microdissection

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Acknowledgements

This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for the Second-Term Comprehensive 10-Year Strategy for Cancer Control. This work was also supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare, and by the Foundation for Promotion of Cancer Research of Japan. We are grateful to Dr Y Hayata of Tokyo Medical College, Japan, for providing us with the PC-14 cell line. Cell lines were also obtained from ATCC. K Kobayashi is a recipient of a research resident fellowship from the Foundation for Promotion of Cancer Research.

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Authors and Affiliations

  1. Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan

    Keiko Kobayashi, Michiho Nishioka, Takashi Kohno, Masaki Nakamoto & Jun Yokota

  2. Second Department of Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan

    Keiko Kobayashi & Seiichi Takenoshita

  3. Pathology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan

    Arafumi Maeshima

  4. Genetics Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan

    Kazuhiko Aoyagi & Hiroki Sasaki

  5. First Department of Pathology, Hamamatsu University School of Medicine, 20-1, 1-chome, Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Haruhiko Sugimura

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  1. Keiko Kobayashi
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Correspondence to Jun Yokota.

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Kobayashi, K., Nishioka, M., Kohno, T. et al. Identification of genes whose expression is upregulated in lung adenocarcinoma cells in comparison with type II alveolar cells and bronchiolar epithelial cells in vivo. Oncogene 23, 3089–3096 (2004). https://doi.org/10.1038/sj.onc.1207433

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