1. ¹Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
2. ²Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan
3. ³Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan

Correspondence: Dr T Takahashi, Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. E-mail: tak@med.nagoya-u.ac.jp

⁴These authors contributed equally to the present study

⁵Current address: Cellseed Inc., Shinjuku-ku, Tokyo, Japan

⁶Current address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA

Received 27 April 2005; Revised 30 June 2005; Accepted 4 July 2005; Published online 12 September 2005.

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.