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BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells
Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblottin...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773943/ https://www.ncbi.nlm.nih.gov/pubmed/29239139 http://dx.doi.org/10.1002/cam4.1263 |
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author | Tsui, Ke‐Hung Chiang, Kun‐Chun Lin, Yu‐Hsiang Chang, Kang‐Shuo Feng, Tsui‐Hsia Juang, Horng‐Heng |
author_facet | Tsui, Ke‐Hung Chiang, Kun‐Chun Lin, Yu‐Hsiang Chang, Kang‐Shuo Feng, Tsui‐Hsia Juang, Horng‐Heng |
author_sort | Tsui, Ke‐Hung |
collection | PubMed |
description | Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT‐qPCR, or reporter assays. The (3)H‐thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less‐differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT‐4 cells or transient overexpression of p53 into p53‐mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site‐mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53‐induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN‐knockdown RT‐4 cells. PTEN activity inhibitor (VO‐OHpic) treatment decreased BTG2 expression in RT‐4 and PTEN‐overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer. |
format | Online Article Text |
id | pubmed-5773943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57739432018-02-07 BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells Tsui, Ke‐Hung Chiang, Kun‐Chun Lin, Yu‐Hsiang Chang, Kang‐Shuo Feng, Tsui‐Hsia Juang, Horng‐Heng Cancer Med Cancer Biology Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT‐qPCR, or reporter assays. The (3)H‐thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less‐differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT‐4 cells or transient overexpression of p53 into p53‐mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site‐mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53‐induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN‐knockdown RT‐4 cells. PTEN activity inhibitor (VO‐OHpic) treatment decreased BTG2 expression in RT‐4 and PTEN‐overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer. John Wiley and Sons Inc. 2017-12-13 /pmc/articles/PMC5773943/ /pubmed/29239139 http://dx.doi.org/10.1002/cam4.1263 Text en © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Tsui, Ke‐Hung Chiang, Kun‐Chun Lin, Yu‐Hsiang Chang, Kang‐Shuo Feng, Tsui‐Hsia Juang, Horng‐Heng BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title | BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title_full | BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title_fullStr | BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title_full_unstemmed | BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title_short | BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells |
title_sort | btg2 is a tumor suppressor gene upregulated by p53 and pten in human bladder carcinoma cells |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773943/ https://www.ncbi.nlm.nih.gov/pubmed/29239139 http://dx.doi.org/10.1002/cam4.1263 |
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