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DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas

Oncogene volume 23, pages 1405–1411 (2004)Cite this article

Abstract

The deleted in liver cancer (DLC-1) gene at chromosome 8p21–22 is altered mainly by genomic deletion or aberrant promoter methylation in a large number of human cancers such as breast, liver, colon and prostate and is known to have an inhibitory effect on breast and liver tumor cell growth. Given the high frequency of deletion involving region 8p21–22 in human non-small cell lung carcinoma (NSCLC), we examined alterations of DLC-1 in a series of primary tumors and tumor cell lines and tested effects of DLC-1 on tumor cell growth. A significant decrease or absence of the DLC-1 mRNA expression was found in 95% of primary NSCLC (20/21) and 58% of NSCLC cell lines (11/19). Transcriptional silencing of DLC-1 was primarily associated with aberrant DNA methylation, rather than genomic deletion as 5-aza-2′-deoxycytidine induced reactivation of DLC-1 expression in 82% (9/11) NSCLC cell lines showing downregulated DLC-1. It was further evidenced by an aberrant DLC-1 promoter methylation pattern, which was detected by Southern blotting in 73% (8/11) of NSCLC cell lines with downregulation of the gene. The transfer of DLC-1 into three DLC-1 negative cell lines caused a significant inhibition in cell proliferation and/or a decrease in colony formation. Furthermore, stable transfer of DLC-1 abolished tumorigenicity in nude mice of two cell lines, suggesting that DLC-1 plays a role in NSCLC by acting as a bona fide new tumor suppressor gene.

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Authors and Affiliations

  1. Health Effects Laboratory Division, Laboratory of Genetic Susceptibility, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, 26505, WV, USA

    Bao-Zhu Yuan, Amy M Jefferson, Kimberly T Baldwin & Steven H Reynolds

  2. Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, 20892, MD, USA

    Snorri S Thorgeirsson & Nicholas C Popescu

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  1. Bao-Zhu Yuan
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  2. Amy M Jefferson
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  3. Kimberly T Baldwin
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  4. Snorri S Thorgeirsson
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  5. Nicholas C Popescu
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  6. Steven H Reynolds
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Correspondence to Bao-Zhu Yuan.

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Yuan, BZ., Jefferson, A., Baldwin, K. et al. DLC-1 operates as a tumor suppressor gene in human non-small cell lung carcinomas. Oncogene 23, 1405–1411 (2004). https://doi.org/10.1038/sj.onc.1207291

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