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Journal of Hematology & Oncology

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Open Access 01-12-2014 | Research

DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells

Authors: Qian Chu, Na Han, Xun Yuan, Xin Nie, Hua Wu, Yu Chen, Mingzhou Guo, Shiying Yu, Kongming Wu

Published in: Journal of Hematology & Oncology | Issue 1/2014

Abstract

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.

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Title: DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells
Authors: Qian Chu
Na Han
Xun Yuan
Xin Nie
Hua Wu
Yu Chen
Mingzhou Guo
Shiying Yu
Kongming Wu
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-014-0073-5

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