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Title: Del-1 overexpression potentiates lung cancer cell proliferation and invasion

Abstract

Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays,more » respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells. • Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.« less

Authors:
; ; ;  [1];  [2];  [3];  [1]
  1. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
  2. Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of)
  3. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
22594117
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 468; Journal Issue: 1-2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOVIRUS; ANIMAL TISSUES; APOPTOSIS; BRAIN; CARCINOMAS; CELL PROLIFERATION; FIBROBLASTS; GENES; INFLAMMATION; LEUKOCYTES; LUNGS; MESSENGER-RNA; MUTANTS; PATIENTS; PROTEINS; TRANSCRIPTION; TUMOR CELLS

Citation Formats

Lee, Seung-Hwan, Kim, Dong-Young, Jing, Feifeng, Kim, Hyesoon, Yun, Chae-Ok, Han, Deok-Jong, and Choi, Eun Young, E-mail: choieun@ulsan.ac.kr. Del-1 overexpression potentiates lung cancer cell proliferation and invasion. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.10.159.
Lee, Seung-Hwan, Kim, Dong-Young, Jing, Feifeng, Kim, Hyesoon, Yun, Chae-Ok, Han, Deok-Jong, & Choi, Eun Young, E-mail: choieun@ulsan.ac.kr. Del-1 overexpression potentiates lung cancer cell proliferation and invasion. United States. doi:10.1016/J.BBRC.2015.10.159.
Lee, Seung-Hwan, Kim, Dong-Young, Jing, Feifeng, Kim, Hyesoon, Yun, Chae-Ok, Han, Deok-Jong, and Choi, Eun Young, E-mail: choieun@ulsan.ac.kr. 2015. "Del-1 overexpression potentiates lung cancer cell proliferation and invasion". United States. doi:10.1016/J.BBRC.2015.10.159.
@article{osti_22594117,
title = {Del-1 overexpression potentiates lung cancer cell proliferation and invasion},
author = {Lee, Seung-Hwan and Kim, Dong-Young and Jing, Feifeng and Kim, Hyesoon and Yun, Chae-Ok and Han, Deok-Jong and Choi, Eun Young, E-mail: choieun@ulsan.ac.kr},
abstractNote = {Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells. • Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.},
doi = {10.1016/J.BBRC.2015.10.159},
journal = {Biochemical and Biophysical Research Communications},
number = 1-2,
volume = 468,
place = {United States},
year = 2015,
month =
}
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