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Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway
BACKGROUND: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. METHODS: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the ex...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354287/ https://www.ncbi.nlm.nih.gov/pubmed/32676386 http://dx.doi.org/10.21037/tau.2020.03.02 |
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author | Cai, Qiliang Chen, Yegang Zhang, Dingnrong Pan, Jiancheng Xie, Zunke Ma, Shenze Liu, Chuanfeng Zuo, Jiquan Zhou, Xiaodong Quan, Changyi Xin, Zhongcheng Niu, Yuanjie |
author_facet | Cai, Qiliang Chen, Yegang Zhang, Dingnrong Pan, Jiancheng Xie, Zunke Ma, Shenze Liu, Chuanfeng Zuo, Jiquan Zhou, Xiaodong Quan, Changyi Xin, Zhongcheng Niu, Yuanjie |
author_sort | Cai, Qiliang |
collection | PubMed |
description | BACKGROUND: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. METHODS: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. RESULTS: Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-β1 is responsible for EMT in AR knockout TRAMP tumor cells. CONCLUSIONS: In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell’s EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy. |
format | Online Article Text |
id | pubmed-7354287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-73542872020-07-15 Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway Cai, Qiliang Chen, Yegang Zhang, Dingnrong Pan, Jiancheng Xie, Zunke Ma, Shenze Liu, Chuanfeng Zuo, Jiquan Zhou, Xiaodong Quan, Changyi Xin, Zhongcheng Niu, Yuanjie Transl Androl Urol Original Article BACKGROUND: Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. METHODS: Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. RESULTS: Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-β1 is responsible for EMT in AR knockout TRAMP tumor cells. CONCLUSIONS: In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell’s EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy. AME Publishing Company 2020-06 /pmc/articles/PMC7354287/ /pubmed/32676386 http://dx.doi.org/10.21037/tau.2020.03.02 Text en 2020 Translational Andrology and Urology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Cai, Qiliang Chen, Yegang Zhang, Dingnrong Pan, Jiancheng Xie, Zunke Ma, Shenze Liu, Chuanfeng Zuo, Jiquan Zhou, Xiaodong Quan, Changyi Xin, Zhongcheng Niu, Yuanjie Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title | Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title_full | Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title_fullStr | Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title_full_unstemmed | Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title_short | Loss of epithelial AR increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via TGF-β1/EMT pathway |
title_sort | loss of epithelial ar increase castration resistant stem-like prostate cancer cells and promotes cancer metastasis via tgf-β1/emt pathway |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354287/ https://www.ncbi.nlm.nih.gov/pubmed/32676386 http://dx.doi.org/10.21037/tau.2020.03.02 |
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