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DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells
BACKGROUND: Renal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203876/ https://www.ncbi.nlm.nih.gov/pubmed/25322986 http://dx.doi.org/10.1186/s13045-014-0073-5 |
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author | Chu, Qian Han, Na Yuan, Xun Nie, Xin Wu, Hua Chen, Yu Guo, Mingzhou Yu, Shiying Wu, Kongming |
author_facet | Chu, Qian Han, Na Yuan, Xun Nie, Xin Wu, Hua Chen, Yu Guo, Mingzhou Yu, Shiying Wu, Kongming |
author_sort | Chu, Qian |
collection | PubMed |
description | BACKGROUND: Renal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated. METHODS: Immunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microaraays and correlation with clinic-pathological characteristics was analyzed. In vitro proliferation, apoptosis and in vivo tumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays. RESULTS: Expression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibited in vitro cellular proliferation, S phase progression, clone formation, and in vivo tumor growth. In mechanism, DACH1 repressed cyclin D1 transcription through association with AP-1 protein. CONCLUSION: Our results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy. |
format | Online Article Text |
id | pubmed-4203876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42038762014-10-22 DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells Chu, Qian Han, Na Yuan, Xun Nie, Xin Wu, Hua Chen, Yu Guo, Mingzhou Yu, Shiying Wu, Kongming J Hematol Oncol Research BACKGROUND: Renal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated. METHODS: Immunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microaraays and correlation with clinic-pathological characteristics was analyzed. In vitro proliferation, apoptosis and in vivo tumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays. RESULTS: Expression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibited in vitro cellular proliferation, S phase progression, clone formation, and in vivo tumor growth. In mechanism, DACH1 repressed cyclin D1 transcription through association with AP-1 protein. CONCLUSION: Our results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy. BioMed Central 2014-10-17 /pmc/articles/PMC4203876/ /pubmed/25322986 http://dx.doi.org/10.1186/s13045-014-0073-5 Text en © Chu et al.; licensee BioMed Central Ltd. 2014 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 Chu, Qian Han, Na Yuan, Xun Nie, Xin Wu, Hua Chen, Yu Guo, Mingzhou Yu, Shiying Wu, Kongming DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title | DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title_full | DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title_fullStr | DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title_full_unstemmed | DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title_short | DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells |
title_sort | dach1 inhibits cyclin d1 expression, cellular proliferation and tumor growth of renal cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203876/ https://www.ncbi.nlm.nih.gov/pubmed/25322986 http://dx.doi.org/10.1186/s13045-014-0073-5 |
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