Correlation between histone acetylation and expression of Notch1 in human lung carcinoma and its possible role in combined small-cell lung carcinoma.

Autor: Hassan WA; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.; Department of Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt., Takebayashi SI; Department of Biochemistry and Proteomics, Graduate School of Medicine, Mie University, Mie, Japan., Abdalla MOA; Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt., Fujino K; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.; Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Kudoh S; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Motooka Y; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.; Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Sato Y; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan., Naito Y; Department of Pathology, Kurume University School of Medicine, Kurume, Japan., Higaki K; Division of Pathology, St Mary Hospital, Kurume, Japan., Wakimoto J; Division of Pathology, Minami Kyushu National Hospital, Kagoshima, Japan., Okada S; Department of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan., Nakao M; Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan., Ishikawa Y; Division of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan., Ito T; Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Jazyk: angličtina
Zdroj: Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2017 Aug; Vol. 97 (8), pp. 913-921. Date of Electronic Publication: 2017 Apr 17.
DOI: 10.1038/labinvest.2017.36
Abstrakt: Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating the molecular differences between SCLC and NSCLC could lead to a better understanding of the pathogenesis of such neoplasms. Therefore, in this study, we investigated the correlation between histone acetylation and Notch1 expression in lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the level of acetylated histone H3 around the promoter region of Notch1 in SCLC and NSCLC cells. We then treated SCLC cells with trichostatin A (TSA) and characterized the level of histone H3 acetylation at Notch1. In addition, TSA-treated cells were injected into immune-compromised mice, for analysis of the ex vivo tumor xenograft phenotype. The level of acetylated histone H3 surrounding the Notch1 promoter was lower in lung cancer cells not expressing Notch1. Tumors originated from TSA-treated SCLC cells occasionally formed an epithelial-like glandular arrangement of cells; with Notch1 expression and decreased expression of neuroendocrine (NE) markers. Histone deacetylation around the promoter region of Notch1 inhibits Notch1 protein expression in SCLC and the restoration of Notch1 expression in SCLC leads to the concurrent appearance of epithelial-like areas within the SCLC, which could provide a possible mechanism for histogenesis of cSCLC.
Databáze: MEDLINE
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