Cargando…
Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling
INTRODUCTION: Transducin (β)-like 1 X-linked receptor 1(TBLR1) is an F-box-like and WD repeat-containing protein which functions as a switch in transcriptional activation, However, the clinical significance and biological role of TBLR1 in breast cancer remains largely unknown. METHODS: Western blott...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303137/ https://www.ncbi.nlm.nih.gov/pubmed/25341494 http://dx.doi.org/10.1186/s13058-014-0465-z |
_version_ | 1782353892532551680 |
---|---|
author | Li, Xinghua Liang, Weijiang Liu, Junling Lin, Chuyong Wu, Shu Song, Libing Yuan, Zhongyu |
author_facet | Li, Xinghua Liang, Weijiang Liu, Junling Lin, Chuyong Wu, Shu Song, Libing Yuan, Zhongyu |
author_sort | Li, Xinghua |
collection | PubMed |
description | INTRODUCTION: Transducin (β)-like 1 X-linked receptor 1(TBLR1) is an F-box-like and WD repeat-containing protein which functions as a switch in transcriptional activation, However, the clinical significance and biological role of TBLR1 in breast cancer remains largely unknown. METHODS: Western blotting, immunocytochemistry and real-time PCR were used to evaluate TBLR1 expression in normal breast epithelial cells and breast cancer cell lines, clinical tissue samples and adjacent nontumor tissues, and in 214 paraffin-embedded specimens. Statistical analyses were used to test for the prognostic and diagnostic associations. The biological role of TBLR1 -induced proliferation and tumorigenicity in breast cancer cells was explored in vitro and in vivo. The effect of TBLR1 on the expression of cyclin D1 and β-catenin signaling was examined by Western blotting, luciferase reporter assay and by several immunoprecipitation techniques. RESULTS: TBLR1 was significantly upregulated in breast cancer cells and tissues compared to normal control samples. Immunohistochemical analysis revealed high expression of TBLR1 in 113 of 214 (52.8%) paraffin-embedded archival breast cancer. The overall expression level of TBLR1 was significantly correlated with clinical stage (P <0.001), the tumor classification (P <0.001), node classification (P =0.024), and metastasis classification (P = 0.004), histological grade (P = 0.044), as well as with the expression level of c-erbB2 (P = 0.036) and Ki-67 (P <0.001). Patients with higher TBLR1 expression had shorter overall survival time, whereas patients with lower TBLR1 expression had better survival. Multivariate analysis suggested that TBLR1 expression might be an independent prognostic indicator for the survival of breast cancer patients. TBLR1 overexpression promoted, whereas TBLR1 silencing inhibited, proliferation and tumorigenicity in breast cancer cells both in vitro and in vivo. We found that TBLR1 expression was implicated in the upregulation of cyclin D1, phosphorylation of cell-cycle control protein Rb (pRb) and activation of β-catenin signaling in breast cancer. CONCLUSIONS: TBLR1 plays a key role in the development and progression of breast cancer cells via cyclin D1-transactivation and activation of the β-catenin signaling pathway. TBLR1 may be a novel prognostic marker and a potential therapeutic target in the treatment human breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0465-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4303137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43031372015-01-23 Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling Li, Xinghua Liang, Weijiang Liu, Junling Lin, Chuyong Wu, Shu Song, Libing Yuan, Zhongyu Breast Cancer Res Research Article INTRODUCTION: Transducin (β)-like 1 X-linked receptor 1(TBLR1) is an F-box-like and WD repeat-containing protein which functions as a switch in transcriptional activation, However, the clinical significance and biological role of TBLR1 in breast cancer remains largely unknown. METHODS: Western blotting, immunocytochemistry and real-time PCR were used to evaluate TBLR1 expression in normal breast epithelial cells and breast cancer cell lines, clinical tissue samples and adjacent nontumor tissues, and in 214 paraffin-embedded specimens. Statistical analyses were used to test for the prognostic and diagnostic associations. The biological role of TBLR1 -induced proliferation and tumorigenicity in breast cancer cells was explored in vitro and in vivo. The effect of TBLR1 on the expression of cyclin D1 and β-catenin signaling was examined by Western blotting, luciferase reporter assay and by several immunoprecipitation techniques. RESULTS: TBLR1 was significantly upregulated in breast cancer cells and tissues compared to normal control samples. Immunohistochemical analysis revealed high expression of TBLR1 in 113 of 214 (52.8%) paraffin-embedded archival breast cancer. The overall expression level of TBLR1 was significantly correlated with clinical stage (P <0.001), the tumor classification (P <0.001), node classification (P =0.024), and metastasis classification (P = 0.004), histological grade (P = 0.044), as well as with the expression level of c-erbB2 (P = 0.036) and Ki-67 (P <0.001). Patients with higher TBLR1 expression had shorter overall survival time, whereas patients with lower TBLR1 expression had better survival. Multivariate analysis suggested that TBLR1 expression might be an independent prognostic indicator for the survival of breast cancer patients. TBLR1 overexpression promoted, whereas TBLR1 silencing inhibited, proliferation and tumorigenicity in breast cancer cells both in vitro and in vivo. We found that TBLR1 expression was implicated in the upregulation of cyclin D1, phosphorylation of cell-cycle control protein Rb (pRb) and activation of β-catenin signaling in breast cancer. CONCLUSIONS: TBLR1 plays a key role in the development and progression of breast cancer cells via cyclin D1-transactivation and activation of the β-catenin signaling pathway. TBLR1 may be a novel prognostic marker and a potential therapeutic target in the treatment human breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0465-z) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-24 2014 /pmc/articles/PMC4303137/ /pubmed/25341494 http://dx.doi.org/10.1186/s13058-014-0465-z Text en © Li et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Li, Xinghua Liang, Weijiang Liu, Junling Lin, Chuyong Wu, Shu Song, Libing Yuan, Zhongyu Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title | Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title_full | Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title_fullStr | Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title_full_unstemmed | Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title_short | Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
title_sort | transducin (β)-like 1 x-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303137/ https://www.ncbi.nlm.nih.gov/pubmed/25341494 http://dx.doi.org/10.1186/s13058-014-0465-z |
work_keys_str_mv | AT lixinghua transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT liangweijiang transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT liujunling transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT linchuyong transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT wushu transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT songlibing transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling AT yuanzhongyu transducinblike1xlinkedreceptor1promotesproliferationandtumorigenicityinhumanbreastcancerviaactivationofbetacateninsignaling |