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Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice
Lung cancer is the most common cause of cancer-related death worldwide. A poor overall survival rate of 16% necessitates the need for novel treatment strategies. Mouse models of lung cancer are important tools for analyzing the significance of somatic mutations in the initiation and progression of l...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519541/ https://www.ncbi.nlm.nih.gov/pubmed/23251519 http://dx.doi.org/10.1371/journal.pone.0051400 |
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author | Linnerth-Petrik, Nicolle M. Santry, Lisa A. Yu, Darrick L. Wootton, Sarah K. |
author_facet | Linnerth-Petrik, Nicolle M. Santry, Lisa A. Yu, Darrick L. Wootton, Sarah K. |
author_sort | Linnerth-Petrik, Nicolle M. |
collection | PubMed |
description | Lung cancer is the most common cause of cancer-related death worldwide. A poor overall survival rate of 16% necessitates the need for novel treatment strategies. Mouse models of lung cancer are important tools for analyzing the significance of somatic mutations in the initiation and progression of lung cancer. Of additional importance, however, are animal models of virally induced cancers. JSRV is a simple betaretrovirus that causes contagious lung cancer in sheep known as ovine pulmonary adenocarcinoma and closely resembles human lung adenocarcinoma. Previously we showed that expression of the JSRV envelope (Env) from an AAV vector induced lung tumors in immunodeficient mice, but not in immunocompetent mice. Because of the importance of studying lung cancer in the context of an intact immune system we sought to improve our mouse model. In this report, we employed the use of a strong JSRV enhancer-promoter combination to express Env at high levels and demonstrate for the first time, lung tumor induction in immunocompetent mice. This occurred despite a robust Env-specific antibody-mediated immune response. The PI3K/Akt and MAPK pathways were activated in both immunocompetent and immunodeficient mice, however, differential activation of PTEN, GSKα, p70S6K, p38MAPK, ATF2 and STAT5 was observed. A JSRV Env lung tumor-derived cell line was shown to have a similar signal transduction activation profile as Env-induced lung tumors in C57BL/6 mice. Given the similarities between our model and pulmonary adenocarcinomas in humans, and the ease with which tumors can be induced in any transgenic mouse, this system can be used to uncover novel mechanisms involved lung tumorigenesis. |
format | Online Article Text |
id | pubmed-3519541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35195412012-12-18 Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice Linnerth-Petrik, Nicolle M. Santry, Lisa A. Yu, Darrick L. Wootton, Sarah K. PLoS One Research Article Lung cancer is the most common cause of cancer-related death worldwide. A poor overall survival rate of 16% necessitates the need for novel treatment strategies. Mouse models of lung cancer are important tools for analyzing the significance of somatic mutations in the initiation and progression of lung cancer. Of additional importance, however, are animal models of virally induced cancers. JSRV is a simple betaretrovirus that causes contagious lung cancer in sheep known as ovine pulmonary adenocarcinoma and closely resembles human lung adenocarcinoma. Previously we showed that expression of the JSRV envelope (Env) from an AAV vector induced lung tumors in immunodeficient mice, but not in immunocompetent mice. Because of the importance of studying lung cancer in the context of an intact immune system we sought to improve our mouse model. In this report, we employed the use of a strong JSRV enhancer-promoter combination to express Env at high levels and demonstrate for the first time, lung tumor induction in immunocompetent mice. This occurred despite a robust Env-specific antibody-mediated immune response. The PI3K/Akt and MAPK pathways were activated in both immunocompetent and immunodeficient mice, however, differential activation of PTEN, GSKα, p70S6K, p38MAPK, ATF2 and STAT5 was observed. A JSRV Env lung tumor-derived cell line was shown to have a similar signal transduction activation profile as Env-induced lung tumors in C57BL/6 mice. Given the similarities between our model and pulmonary adenocarcinomas in humans, and the ease with which tumors can be induced in any transgenic mouse, this system can be used to uncover novel mechanisms involved lung tumorigenesis. Public Library of Science 2012-12-10 /pmc/articles/PMC3519541/ /pubmed/23251519 http://dx.doi.org/10.1371/journal.pone.0051400 Text en © 2012 Linnerth-Petrik et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Linnerth-Petrik, Nicolle M. Santry, Lisa A. Yu, Darrick L. Wootton, Sarah K. Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title | Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title_full | Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title_fullStr | Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title_full_unstemmed | Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title_short | Adeno-Associated Virus Vector Mediated Expression of an Oncogenic Retroviral Envelope Protein Induces Lung Adenocarcinomas in Immunocompetent Mice |
title_sort | adeno-associated virus vector mediated expression of an oncogenic retroviral envelope protein induces lung adenocarcinomas in immunocompetent mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519541/ https://www.ncbi.nlm.nih.gov/pubmed/23251519 http://dx.doi.org/10.1371/journal.pone.0051400 |
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