Cargando…

Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura

Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B(1) (BDKRB1) and B(2) (BDKRB2) receptors. The development and progression of cancer results from...

Descripción completa

Detalles Bibliográficos
Autores principales: Wong, Joshua, Sia, Yee Yen, Misso, Neil L., Aggarwal, Shashi, Ng, Angeline, Bhoola, Kanti D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166727/
https://www.ncbi.nlm.nih.gov/pubmed/21904690
http://dx.doi.org/10.4061/2011/167046
_version_ 1782211175485800448
author Wong, Joshua
Sia, Yee Yen
Misso, Neil L.
Aggarwal, Shashi
Ng, Angeline
Bhoola, Kanti D.
author_facet Wong, Joshua
Sia, Yee Yen
Misso, Neil L.
Aggarwal, Shashi
Ng, Angeline
Bhoola, Kanti D.
author_sort Wong, Joshua
collection PubMed
description Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B(1) (BDKRB1) and B(2) (BDKRB2) receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers.
format Online
Article
Text
id pubmed-3166727
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher SAGE-Hindawi Access to Research
record_format MEDLINE/PubMed
spelling pubmed-31667272011-09-08 Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura Wong, Joshua Sia, Yee Yen Misso, Neil L. Aggarwal, Shashi Ng, Angeline Bhoola, Kanti D. Patholog Res Int Research Article Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B(1) (BDKRB1) and B(2) (BDKRB2) receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers. SAGE-Hindawi Access to Research 2011 2011-09-04 /pmc/articles/PMC3166727/ /pubmed/21904690 http://dx.doi.org/10.4061/2011/167046 Text en Copyright © 2011 Joshua Wong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wong, Joshua
Sia, Yee Yen
Misso, Neil L.
Aggarwal, Shashi
Ng, Angeline
Bhoola, Kanti D.
Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title_full Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title_fullStr Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title_full_unstemmed Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title_short Effects of the Demethylating Agent, 5-Azacytidine, on Expression of the Kallikrein-Kinin Genes in Carcinoma Cells of the Lung and Pleura
title_sort effects of the demethylating agent, 5-azacytidine, on expression of the kallikrein-kinin genes in carcinoma cells of the lung and pleura
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166727/
https://www.ncbi.nlm.nih.gov/pubmed/21904690
http://dx.doi.org/10.4061/2011/167046
work_keys_str_mv AT wongjoshua effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura
AT siayeeyen effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura
AT missoneill effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura
AT aggarwalshashi effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura
AT ngangeline effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura
AT bhoolakantid effectsofthedemethylatingagent5azacytidineonexpressionofthekallikreinkiningenesincarcinomacellsofthelungandpleura