title: Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma.
abstract: OBJECTIVE
  The role of Notch signaling in human lung cancer still remains unclear, and there has been and stills a debate, on the extent to which Notch ligands and receptors are involved in lung cancer development. This study was carried out to investigate the role of Notch1 signaling in the proliferation and differentiation of human lung cancer cells.
  
  
  METHODS
  We used small interfering RNA (siRNA) technology to down-regulate the expression of Notch1 in small cell lung carcinoma (SCLC) cells; H69AR and SBC-3, as well as in non-small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC) and H2170 squamous cell carcinoma (SCC). Also, we transfected venus Notch1 intracellular domain (v.NICD) plasmid into the human SCLC line H69 and H1688. In addition, H1688 cells with activated Notch1 were injected into immune-compromised Rag2(-/-) Jak3(-/-) mice for analysis of ex vivo tumor growth and differentiation phenotype.
  
  
  RESULTS
  Notch1 controls cell proliferation and apoptosis in both SCLC and A549; but not in H2170 cell line. Overexpression of Notch1 in SCLC markedly decreased cell proliferation via apoptosis. The subcutaneous tumors arising from xenotransplaned SCLC cells transfected with Notch1 showed "epithelial-like glandular" arrangement, with positive Alcian blue staining and reduction in neuroendocrine markers.
  
  
  CONCLUSIONS
  Notch1 up regulation has an inhibitory effect on cell growth and NE differentiation in SCLC, with induction of an epithelial-like morphology of cells in tissue samples. In NSCLC, Notch1 expression has a tumor inhibitory effect on ADC cells, but not SCC cells.
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan; Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Hassan
authors.initials: H
authors.lastname: Wael
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Kohki
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Niimori-Kita
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan. Electronic address: takaito@kumamoto-u.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D060787:Neoplasm Grading; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology
chemical_list: D051881:Receptor, Notch1
keywords: Apoptosis; Cell proliferation; Epithelial phenotype; Human lung carcinoma; Neuro-endocrine differentiation; Notch1 signaling