title: Stratifin accelerates progression of lung adenocarcinoma at an early stage.
abstract: BACKGROUND
  Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal outcome. We had previously compared the expression profiles of AIS with those of eIA showing lymph node metastasis or a fatal outcome, and found that stratifin (SFN, 14-3-3 sigma) was a differentially expressed gene related to cell proliferation. Here, we performed an in vivo study to clarify the role of SFN in initiation and progression of lung adenocarcinoma.
  
  
  RESULTS
  Suppression of SFN expression in A549 (a human lung adenocarcinoma cell line) by siSFN significantly reduced cell proliferation activity and the S-phase subpopulation. In vivo, tumor development or metastasis to the lung was reduced in shSFN-transfected A549 cells. Moreover, we generated SFN-transgenic mice (Tg-SPC-SFN(+/-)) showing lung-specific expression of human SFN under the control of a tissue-specific enhancer, the SPC promoter. We found that Tg-SPC-SFN(+/-) mice developed lung tumors at a significantly higher rate than control mice after administration of chemical carcinogen, NNK. Interestingly, several Tg-SPC-SFN(+/-) mice developed tumors without NNK. These tumor cells showed high hSFN expression.
  
  
  CONCLUSIONS
  These results suggest that SFN facilitates lung tumor development and progression. SFN appears to be a novel oncogene with potential as a therapeutic target.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. aya_shiba@md.tsukuba.ac.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Shiba-Ishii
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. heka918@gmail.com.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. bgnkn946@yahoo.co.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shiozawa
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. pwtjw085@yahoo.co.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Iyama
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. satomi.kaishi@gmail.com.
authors.forename: Kaishi
authors.initials: K
authors.lastname: Satomi
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. junkano@md.tsukuba.ac.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Kano
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. sakashingo@hotmail.com.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakashita
authors.affiliation: Department of Pathology, Tokyo Medical University Ibaraki Medical Center, Inashiki-gun, Ibaraki, Japan. ymorishi@tokyo-med.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, 305-8575, Japan. nmasayuk@md.tsukuba.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D018450:Disease Progression; D005095:Exoribonucleases / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009602:Nitrosamines / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D005095:Exoribonucleases; C413442:SFN protein, human