title: Identification of frequent G(2) checkpoint impairment and a homozygous deletion of 14-3-3epsilon at 17p13.3 in small cell lung cancers.
abstract: Accumulating evidence suggests that a coordinately controlled G(2) 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 14-3-3epsilon 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 14-3-3epsilon induced significantly restored G(2) checkpoint responses, which resulted in the reduction of mitotic cells as well as of aberrant mitotic figures in the X-ray-irradiated 14-3-3epsilon-null small cell lung cancer cell line. Interestingly, we also found that the G(2) 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 G(2) checkpoint in the pathogenesis of this aggressive form of human lung cancers.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Harano
authors.forename: Kotaro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.forename: Akira
authors.initials: A
authors.lastname: Masuda
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D048948:14-3-3 Proteins; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D016195:G2 Phase / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008938:Mitosis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D014446:Tyrosine 3-Monooxygenase