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Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer
Previously, mapping of the 9p23-24 amplicon in esophageal cancer cell lines led us to the positional cloning of GASC1 (gene amplified in squamous cell carcinoma 1), which encodes a nuclear protein with a Jumonji C (JmjC) domain that catalyzes lysine (K) demethylation of histones. However, the transf...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795798/ https://www.ncbi.nlm.nih.gov/pubmed/19784073 http://dx.doi.org/10.1038/onc.2009.297 |
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author | Liu, Gang Bollig-Fischer, Aliccia Kreike, Bas van de Vijver, Marc J. Abrams, Judith Ethier, Stephen P. Yang, Zeng-Quan |
author_facet | Liu, Gang Bollig-Fischer, Aliccia Kreike, Bas van de Vijver, Marc J. Abrams, Judith Ethier, Stephen P. Yang, Zeng-Quan |
author_sort | Liu, Gang |
collection | PubMed |
description | Previously, mapping of the 9p23-24 amplicon in esophageal cancer cell lines led us to the positional cloning of GASC1 (gene amplified in squamous cell carcinoma 1), which encodes a nuclear protein with a Jumonji C (JmjC) domain that catalyzes lysine (K) demethylation of histones. However, the transforming roles of GASC1 in breast cancer remain to be determined. In this study, we identified GASC1 as one of the amplified genes for the 9p23-24 region in breast cancer, particularly in basal-like subtypes. The levels of GASC1 transcript expression were significantly higher in aggressive, basal-like breast cancers compared with non basal-like breast cancers. Our in vitro assays demonstrated that GASC1 induces transformed phenotypes, including growth factor-independent proliferation, anchorage-independent growth, altered morphogenesis in Matrigel, and mammosphere forming ability, when over expressed in immortalized, nontransformed mammary epithelial MCF10A cells. Additionally, GASC1 demethylase activity regulates the expression of genes critical for stem cell self-renewal, including NOTCH1, and may be linked to the stem cell phenotypes in breast cancer. Thus, GASC1 is a driving oncogene in the 9p23-24 amplicon in human breast cancer and targeted inhibition of GASC1 histone demethylase in cancer could provide potential new avenues for therapeutic development. |
format | Text |
id | pubmed-2795798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-27957982010-06-17 Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer Liu, Gang Bollig-Fischer, Aliccia Kreike, Bas van de Vijver, Marc J. Abrams, Judith Ethier, Stephen P. Yang, Zeng-Quan Oncogene Article Previously, mapping of the 9p23-24 amplicon in esophageal cancer cell lines led us to the positional cloning of GASC1 (gene amplified in squamous cell carcinoma 1), which encodes a nuclear protein with a Jumonji C (JmjC) domain that catalyzes lysine (K) demethylation of histones. However, the transforming roles of GASC1 in breast cancer remain to be determined. In this study, we identified GASC1 as one of the amplified genes for the 9p23-24 region in breast cancer, particularly in basal-like subtypes. The levels of GASC1 transcript expression were significantly higher in aggressive, basal-like breast cancers compared with non basal-like breast cancers. Our in vitro assays demonstrated that GASC1 induces transformed phenotypes, including growth factor-independent proliferation, anchorage-independent growth, altered morphogenesis in Matrigel, and mammosphere forming ability, when over expressed in immortalized, nontransformed mammary epithelial MCF10A cells. Additionally, GASC1 demethylase activity regulates the expression of genes critical for stem cell self-renewal, including NOTCH1, and may be linked to the stem cell phenotypes in breast cancer. Thus, GASC1 is a driving oncogene in the 9p23-24 amplicon in human breast cancer and targeted inhibition of GASC1 histone demethylase in cancer could provide potential new avenues for therapeutic development. 2009-09-28 2009-12-17 /pmc/articles/PMC2795798/ /pubmed/19784073 http://dx.doi.org/10.1038/onc.2009.297 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Liu, Gang Bollig-Fischer, Aliccia Kreike, Bas van de Vijver, Marc J. Abrams, Judith Ethier, Stephen P. Yang, Zeng-Quan Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title | Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title_full | Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title_fullStr | Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title_full_unstemmed | Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title_short | Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer |
title_sort | genomic amplification and oncogenic properties of the gasc1 histone demethylase gene in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795798/ https://www.ncbi.nlm.nih.gov/pubmed/19784073 http://dx.doi.org/10.1038/onc.2009.297 |
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