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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma
Lung Cancer, Volume 85, No. 2, Year 2014
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Description
Objectives: 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. Conclusion: 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. © 2014 Elsevier Ireland Ltd.
Authors & Co-Authors
Wael, Hassan
Japan, Kumamoto
Kumamoto University
Egypt, Ismailia
Faculty of Medicine
Yoshida, Ryoji
Japan, Kumamoto
Kumamoto University
Kudoh, Shinji
Japan, Kumamoto
Kumamoto University
Hasegawa, Kohki
Japan, Kumamoto
Kumamoto University
Niimori-Kita, Kanako
Japan, Kumamoto
Kumamoto University
Ito, Takaaki
Japan, Kumamoto
Kumamoto University
Statistics
Citations: 107
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1016/j.lungcan.2014.05.001
ISSN:
01695002
e-ISSN:
18728332
Research Areas
Cancer