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Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism
BACKGROUND: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknow...
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/PMC3293904/ https://www.ncbi.nlm.nih.gov/pubmed/22403723 http://dx.doi.org/10.1371/journal.pone.0032905 |
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author | Xu, Yong Fang, Fang St. Clair, Daret K. St. Clair, William H. |
author_facet | Xu, Yong Fang, Fang St. Clair, Daret K. St. Clair, William H. |
author_sort | Xu, Yong |
collection | PubMed |
description | BACKGROUND: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy. METHODOLOGY/PRINCIPAL FINDINGS: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa cells with a low endogenous level of RelB (LNCaP) and by RNAi-based knock-down in PCa cells with a high constitutive level of RelB (PC3). The effects of RelB, PSA and IL-8 on the response of PCa to radiation treatment were examined in vitro and in xenograft tumors. RelB regulates PSA and IL-8 in an inverse manner. When the cellular levels of PSA and IL-8 were directly modulated by genetic manipulations or by the addition of recombinant proteins, the results demonstrate that up-regulation of IL-8 enhanced radioresistance of PCa cells and concurrently down-regulated PSA. In contrast, up-regulation of PSA resulted in reduced radioresistance with concurrent down-regulation of IL-8. CONCLUSION/SIGNIFICANCE: RelB plays a critical role in the response of PCa to radiotherapy and the inverse expression of IL-8 and PSA. The results identify a previously unrecognized relationship between IL-8 and PSA in the response of PCa cells to radiotherapy. |
format | Online Article Text |
id | pubmed-3293904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32939042012-03-08 Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism Xu, Yong Fang, Fang St. Clair, Daret K. St. Clair, William H. PLoS One Research Article BACKGROUND: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy. METHODOLOGY/PRINCIPAL FINDINGS: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa cells with a low endogenous level of RelB (LNCaP) and by RNAi-based knock-down in PCa cells with a high constitutive level of RelB (PC3). The effects of RelB, PSA and IL-8 on the response of PCa to radiation treatment were examined in vitro and in xenograft tumors. RelB regulates PSA and IL-8 in an inverse manner. When the cellular levels of PSA and IL-8 were directly modulated by genetic manipulations or by the addition of recombinant proteins, the results demonstrate that up-regulation of IL-8 enhanced radioresistance of PCa cells and concurrently down-regulated PSA. In contrast, up-regulation of PSA resulted in reduced radioresistance with concurrent down-regulation of IL-8. CONCLUSION/SIGNIFICANCE: RelB plays a critical role in the response of PCa to radiotherapy and the inverse expression of IL-8 and PSA. The results identify a previously unrecognized relationship between IL-8 and PSA in the response of PCa cells to radiotherapy. Public Library of Science 2012-03-05 /pmc/articles/PMC3293904/ /pubmed/22403723 http://dx.doi.org/10.1371/journal.pone.0032905 Text en Xu 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 Xu, Yong Fang, Fang St. Clair, Daret K. St. Clair, William H. Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title | Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title_full | Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title_fullStr | Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title_full_unstemmed | Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title_short | Inverse Relationship between PSA and IL-8 in Prostate Cancer: An Insight into a NF-κB-Mediated Mechanism |
title_sort | inverse relationship between psa and il-8 in prostate cancer: an insight into a nf-κb-mediated mechanism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293904/ https://www.ncbi.nlm.nih.gov/pubmed/22403723 http://dx.doi.org/10.1371/journal.pone.0032905 |
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