The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.

<h4>Background</h4>The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development.<h4>Methodology/principal findings</h4>Gene copy number was systematically assessed with an ult...

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Autores principales:	Aude Legoffic, Ezequiel Calvo, Carla Cano, Emma Folch-Puy, Marc Barthet, Jean Robert Delpero, Montse Ferrés-Masó, Jean Charles Dagorn, Daniel Closa, Juan Iovanna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc1559a63ed048cc98bab0c1436c9839
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spelling	oai:doaj.org-article:cc1559a63ed048cc98bab0c1436c98392021-11-25T06:28:41ZThe reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.1932-620310.1371/journal.pone.0007495https://doaj.org/article/cc1559a63ed048cc98bab0c1436c98392009-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19834624/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development.<h4>Methodology/principal findings</h4>Gene copy number was systematically assessed with an ultra-high resolution CGH oligonucleotide microarray in DNA from samples of pancreatic cancer. Several new cancer-associated variations were observed. In this work we focused on one of them, involving the reg4 gene. Gene copy number gain of the reg4 gene was confirmed by qPCR in 14 cancer samples. It was also found with increased copy number in most PanIN3 samples. The relationship betweena gain in reg4 gene copy number and cancer development was investigated on the human pancreatic cancer cell line Mia-PaCa2 xenografted under the skin of nude mice. When cells were transfected with a vector allowing reg4 expression, they generated tumors almost twice larger in size. In addition, these tumors were more resistant to gemcitabine treatment than control tumors. Interestingly, weekly intraperitoneal administration of a monoclonal antibody to reg4 halved the size of tumors generated by Mia-PaCa2 cells, suggesting that the antibody interfered with a paracrine/autocrine mechanism involving reg4 and stimulating cancer progression. The addition of gemcitabine resulted in further reduction, tumors becoming 5 times smaller than control. Exposure to reg4 antibody resulted in a significant decrease in intra-tumor levels of pAkt, Bcl-xL, Bcl-2, survivin and cyclin D1.<h4>Conclusions/significance</h4>It was concluded that adjuvant therapies targeting reg4 could improve the standard treatment of pancreatic cancer with gemcitabine.Aude LegofficEzequiel CalvoCarla CanoEmma Folch-PuyMarc BarthetJean Robert DelperoMontse Ferrés-MasóJean Charles DagornDaniel ClosaJuan IovannaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 10, p e7495 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aude Legoffic Ezequiel Calvo Carla Cano Emma Folch-Puy Marc Barthet Jean Robert Delpero Montse Ferrés-Masó Jean Charles Dagorn Daniel Closa Juan Iovanna The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
description	<h4>Background</h4>The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development.<h4>Methodology/principal findings</h4>Gene copy number was systematically assessed with an ultra-high resolution CGH oligonucleotide microarray in DNA from samples of pancreatic cancer. Several new cancer-associated variations were observed. In this work we focused on one of them, involving the reg4 gene. Gene copy number gain of the reg4 gene was confirmed by qPCR in 14 cancer samples. It was also found with increased copy number in most PanIN3 samples. The relationship betweena gain in reg4 gene copy number and cancer development was investigated on the human pancreatic cancer cell line Mia-PaCa2 xenografted under the skin of nude mice. When cells were transfected with a vector allowing reg4 expression, they generated tumors almost twice larger in size. In addition, these tumors were more resistant to gemcitabine treatment than control tumors. Interestingly, weekly intraperitoneal administration of a monoclonal antibody to reg4 halved the size of tumors generated by Mia-PaCa2 cells, suggesting that the antibody interfered with a paracrine/autocrine mechanism involving reg4 and stimulating cancer progression. The addition of gemcitabine resulted in further reduction, tumors becoming 5 times smaller than control. Exposure to reg4 antibody resulted in a significant decrease in intra-tumor levels of pAkt, Bcl-xL, Bcl-2, survivin and cyclin D1.<h4>Conclusions/significance</h4>It was concluded that adjuvant therapies targeting reg4 could improve the standard treatment of pancreatic cancer with gemcitabine.
format	article
author	Aude Legoffic Ezequiel Calvo Carla Cano Emma Folch-Puy Marc Barthet Jean Robert Delpero Montse Ferrés-Masó Jean Charles Dagorn Daniel Closa Juan Iovanna
author_facet	Aude Legoffic Ezequiel Calvo Carla Cano Emma Folch-Puy Marc Barthet Jean Robert Delpero Montse Ferrés-Masó Jean Charles Dagorn Daniel Closa Juan Iovanna
author_sort	Aude Legoffic
title	The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
title_short	The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
title_full	The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
title_fullStr	The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
title_full_unstemmed	The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
title_sort	reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/cc1559a63ed048cc98bab0c1436c9839
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The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target.

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