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Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells

The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction...

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Autores principales: Muñoz, Juan Pablo, González, Carolina, Parra, Bárbara, Corvalán, Alejandro H., Tornesello, Maria Lina, Eizuru, Yoshito, Aguayo, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360647/
https://www.ncbi.nlm.nih.gov/pubmed/22662279
http://dx.doi.org/10.1371/journal.pone.0038178
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author Muñoz, Juan Pablo
González, Carolina
Parra, Bárbara
Corvalán, Alejandro H.
Tornesello, Maria Lina
Eizuru, Yoshito
Aguayo, Francisco
author_facet Muñoz, Juan Pablo
González, Carolina
Parra, Bárbara
Corvalán, Alejandro H.
Tornesello, Maria Lina
Eizuru, Yoshito
Aguayo, Francisco
author_sort Muñoz, Juan Pablo
collection PubMed
description The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16(INK4A) overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation.
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spelling pubmed-33606472012-06-01 Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells Muñoz, Juan Pablo González, Carolina Parra, Bárbara Corvalán, Alejandro H. Tornesello, Maria Lina Eizuru, Yoshito Aguayo, Francisco PLoS One Research Article The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16(INK4A) overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation. Public Library of Science 2012-05-25 /pmc/articles/PMC3360647/ /pubmed/22662279 http://dx.doi.org/10.1371/journal.pone.0038178 Text en Muñoz 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
Muñoz, Juan Pablo
González, Carolina
Parra, Bárbara
Corvalán, Alejandro H.
Tornesello, Maria Lina
Eizuru, Yoshito
Aguayo, Francisco
Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title_full Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title_fullStr Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title_full_unstemmed Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title_short Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
title_sort functional interaction between human papillomavirus type 16 e6 and e7 oncoproteins and cigarette smoke components in lung epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360647/
https://www.ncbi.nlm.nih.gov/pubmed/22662279
http://dx.doi.org/10.1371/journal.pone.0038178
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