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Aberrant methylation of SPARC in human lung cancers
SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca(2+)-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinic...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361924/ https://www.ncbi.nlm.nih.gov/pubmed/15756262 http://dx.doi.org/10.1038/sj.bjc.6602376 |
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author | Suzuki, M Hao, C Takahashi, T Shigematsu, H Shivapurkar, N Sathyanarayana, U G Iizasa, T Fujisawa, T Hiroshima, K Gazdar, A F |
author_facet | Suzuki, M Hao, C Takahashi, T Shigematsu, H Shivapurkar, N Sathyanarayana, U G Iizasa, T Fujisawa, T Hiroshima, K Gazdar, A F |
author_sort | Suzuki, M |
collection | PubMed |
description | SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca(2+)-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75–12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers. |
format | Text |
id | pubmed-2361924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23619242009-09-10 Aberrant methylation of SPARC in human lung cancers Suzuki, M Hao, C Takahashi, T Shigematsu, H Shivapurkar, N Sathyanarayana, U G Iizasa, T Fujisawa, T Hiroshima, K Gazdar, A F Br J Cancer Molecular Diagnostics SPARC (secreted protein acidic and rich in cysteine) is an extracellular Ca(2+)-binding matricellular glycoprotein associated with the regulation of cell adhesion and growth. We investigated loss of expression of SPARC gene and promoter methylation in lung cancers and correlated the data with clinicopathological features. We observed loss of SPARC expression in 12 of 20 (60%) lung cancer cell lines. Treatment of expression-negative cell lines with a demethylating agent restored expression in all cases. Methylation frequencies of SPARC gene were 55% in 20 lung cancer cell lines. Primary tumours had methylation at a rate of 69% (119 of 173), while nonmalignant lung tissues (n=60) had very low rates (3%). In lung adenocarcinomas, SPARC methylation correlated with a negative prognosis (P=0.0021; relative risk 4.65, 95% confidence interval 1.75–12.35, multivariate Cox's proportional-hazard model). Immunostaining revealed protein expression in bronchial epithelium (weak intensity) and in juxtatumoral stromal tissues (strong intensity) accompanied by frequent loss in cancer cells that correlated with the presence of methylation (P<0.001). Our findings are of biological interest and potentially of clinical importance in human lung cancers. Nature Publishing Group 2005-03-14 2005-03-01 /pmc/articles/PMC2361924/ /pubmed/15756262 http://dx.doi.org/10.1038/sj.bjc.6602376 Text en Copyright © 2005 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular Diagnostics Suzuki, M Hao, C Takahashi, T Shigematsu, H Shivapurkar, N Sathyanarayana, U G Iizasa, T Fujisawa, T Hiroshima, K Gazdar, A F Aberrant methylation of SPARC in human lung cancers |
title | Aberrant methylation of SPARC in human lung cancers |
title_full | Aberrant methylation of SPARC in human lung cancers |
title_fullStr | Aberrant methylation of SPARC in human lung cancers |
title_full_unstemmed | Aberrant methylation of SPARC in human lung cancers |
title_short | Aberrant methylation of SPARC in human lung cancers |
title_sort | aberrant methylation of sparc in human lung cancers |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361924/ https://www.ncbi.nlm.nih.gov/pubmed/15756262 http://dx.doi.org/10.1038/sj.bjc.6602376 |
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