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Journal of Cancer Research and Clinical Oncology

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01-06-2019 | Prostate Cancer | Original Article – Cancer Research

IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2

Authors: Xiaodong Chen, Feng Chen, Yu Ren, Guobin Weng, Lijun Xu, Xiang Xue, Peter C. Keng, Soo Ok Lee, Yuhchyau Chen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 6/2019

Abstract

Purpose

To study an association between IL-6 signaling and resistance to radiotherapy of prostate cancer (PCa) and explore the molecular mechanisms involved.

Methods

IL-6 expressing C4-2 and CWR22Rv1 (C4-2IL-6/CWRIL-6) and vector control (C4-2vec/CWRvec) cell lines were developed. Radiation-sensitivities of these cells were compared in clonogenic assay, Comet assay, and γH2AX staining. In xenograft animal studies, radiation-sensitivity of C4-2IL-6 cell-derived tumors vs. C4-2vec cell-derived tumors was investigated. To reveal IL-6 downstream molecules involved in DNA repair after radiation, qPCR and Western blot analyses as well as immunofluorescence staining were performed. Transcriptional control of IL-6 on ATM and ATR molecules was also investigated.

Results

We found C4-2IL-6 and CWRIL-6 cells survived better than their vector control cells after irradiation, and animal studies confirmed such in vitro results. We discovered that DNA repair-related molecules such as ATM, ATR, BRCA1, and BRCA2 were significantly upregulated in irradiated IL-6 expressing cells compared with vector control cells. We further defined that IL-6 signaling regulated cellular expressions of ATM and ATR at the transcriptional level through the activation of Stat3 signaling pathway.

Conclusions

IL-6 leads to PCa resistance to radiation through upregulation of DNA repair associated molecules ATM, ATR, BRCA1, and BRCA2.

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Title: IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2
Authors: Xiaodong Chen
Feng Chen
Yu Ren
Guobin Weng
Lijun Xu
Xiang Xue
Peter C. Keng
Soo Ok Lee
Yuhchyau Chen
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 6/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02917-z

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IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

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