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Identification of Frequent G₂ Checkpoint Impairment and a Homozygous Deletion of 14-3-3 at 17p13.3 in Small Cell Lung Cancers¹

Division of Molecular Oncology, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464-8681 [H. K., T. N., T. H., K. M., H. S., A. M., H. O., T. T.], and Department of Surgery, Osaka University Graduate School of Medicine, Yamadaoka, Suita 565-0871 [H. K., H. M.], Japan

Accumulating evidence suggests that a coordinately controlled G₂ checkpoint prevents cells with damaged DNA from entering mitosis, thus playing an important role in the maintenance of chromosomal integrity. In the study presented here, we identified a homozygous deletion of the 14-3-3 gene, which resides within a previously identified, commonly deleted region at 17p13.3 in lung cancers, in two small cell lung cancer cell lines that originate from distinct metastatic sites of the same patients. The introduction of 14-3-3 induced significantly restored G₂ checkpoint responses, which resulted in the reduction of mitotic cells as well as of aberrant mitotic figures in the X-ray-irradiated 14-3-3-null small cell lung cancer cell line. Interestingly, we also found that the G₂ checkpoint response is frequently impaired to various degrees in a large fraction of small cell lung cancer cell lines. These findings suggest the possible involvement of the perturbed G₂ checkpoint in the pathogenesis of this aggressive form of human lung cancers.

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