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The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer

Oncogene volume 24, pages 4873–4882 (2005)Cite this article

Abstract

Environmental or occupational exposure to mineral dusts, mainly silica and asbestos, is associated with an increased incidence of lung inflammation, fibrosis, and/or cancer. To better understand the molecular events associated with these pulmonary diseases, we attempted to identify genes that are regulated by mineral dusts. Using a differential display reverse transcription polymerase chain reaction technique and mRNAs of alveolar macrophages from both normal individuals and coal miners, we identified a novel mineral dust-induced gene named mdig, which had not been fully characterized. The expression of mdig mRNA was detected in alveolar macrophages from coal miners but not from normal subjects. The inducible expression of mdig could be observed in A549 cells exposed to silica particles in a time-dependent manner. The full-length mdig mRNA was expressed in human lung cancer tissues but was barely detectable in the adjacent normal tissues. In addition, a number of lung cancer cell lines constitutively express mdig. Alternative spliced transcripts of mdig were detected in some lung cancer cell lines. Silencing mdig mRNA expression in A549 lung cancer cells by siRNA-mediated RNA interference inhibits cell proliferation and sensitizes the cells to silica-induced cytotoxicity. These results suggest that the mdig gene may be involved in the regulation of cell growth and possibly the development of cancer.

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Acknowledgements

This work was partially supported by the United States Bureau of Mines, Generic Mineral Technology Center for Respiratory Dust Grant G1145242 to LM Demers and a Career Development Award under a cooperative agreement from the Centers for Disease Control and Prevention through the Association of Teachers of Preventive Medicine to F Chen. The DDRT–PCR, cloning, and DNA sequencing were conducted by Y Lu and F Chen when both of them were employees of the Pennsylvania State University College of Medicine at Hershey during July, 1994 to June, 1998. We thank Dr Murali Rao and Mr Terry Meighan in the Pathology and Physiology Research Branch at the National Institute for Occupational Safety and Health for their gift of total RNA from A549 cells and the mdig siRNA they purchased.

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  1. Yadong Zhang and Yongju Lu: These authors contributed equally to this paper

Authors and Affiliations

  1. Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China

    Yadong Zhang

  2. The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA

    Yongju Lu, Bao-Zhu Yuan, Vince Castranova, Xianglin Shi & Fei Chen

  3. Departemnt of Medicine, The Pennsylvania State University College of Medicine, Hershey, 17033, PA, USA

    John L Stauffer & Laurence M Demers

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  1. Yadong Zhang
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Corresponding author

Correspondence to Fei Chen.

Additional information

The cDNA sequences reported in this paper have been deposited in the GenBank with access numbers: BE441202, AY302110 and AY456380.

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Zhang, Y., Lu, Y., Yuan, BZ. et al. The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer. Oncogene 24, 4873–4882 (2005). https://doi.org/10.1038/sj.onc.1208668

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