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Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers

Oncogene volume 25, pages 271–277 (2006)Cite this article

Abstract

The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and -independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.

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Acknowledgements

We thank Dr John D Minna for pVcos-7neo-c-jun, Dr Curtis C Harris (National Cancer Center Institute) for BEAS-2B cells, Dr Jun Yokota (National Cancer Center Research Institute) for pTA-hyg and pT2GN, Dr Masatoshi Fujita for pLfosSN (National Cancer Center Research Institute) and Dr Motoshi Suzuki for critical reading of this manuscript. Grant support: This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science.

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Author notes

  1. A Masuda

    Present address: Cellseed Inc., Shinjuku-ku, Tokyo, Japan

  2. H Konishi

    Present address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA

  3. K Maeno and A Masuda: These authors contributed equally to the present study

Authors and Affiliations

  1. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    K Maeno, K Yanagisawa & T Takahashi

  2. Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan

    A Masuda, H Konishi, H Osada & T Saito

  3. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan

    K Maeno & R Ueda

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  1. K Maeno
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Correspondence to T Takahashi.

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Maeno, K., Masuda, A., Yanagisawa, K. et al. Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers. Oncogene 25, 271–277 (2006). https://doi.org/10.1038/sj.onc.1209018

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