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Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2019

24.04.2019 | 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

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

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2019

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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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Literatur
Zurück zum Zitat Bunz F (2016) Principles of cancer genetics. Anticancer Res 36:4979 Bunz F (2016) Principles of cancer genetics. Anticancer Res 36:4979
Zurück zum Zitat Culig Z, Bartsch G, Hobisch A (2002) Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Mol Cell Endocrinol 197:231–238CrossRefPubMed Culig Z, Bartsch G, Hobisch A (2002) Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Mol Cell Endocrinol 197:231–238CrossRefPubMed
Zurück zum Zitat Hayden AJ, Catton C, Pickles T (2010) Radiation therapy in prostate cancer: a risk-adapted strategy. Curr Oncol 17(Suppl 2):S18–S24PubMedPubMedCentral Hayden AJ, Catton C, Pickles T (2010) Radiation therapy in prostate cancer: a risk-adapted strategy. Curr Oncol 17(Suppl 2):S18–S24PubMedPubMedCentral
Zurück zum Zitat Lin DL, Whitney MC, Yao Z, Keller ET (2001) Interleukin-6 induces responsiveness in prostate cancer cells through up-regulation of androgen receptor expression. Clin Cancer Res 7:1773–1781PubMed Lin DL, Whitney MC, Yao Z, Keller ET (2001) Interleukin-6 induces responsiveness in prostate cancer cells through up-regulation of androgen receptor expression. Clin Cancer Res 7:1773–1781PubMed
Zurück zum Zitat Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191CrossRefPubMed Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191CrossRefPubMed
Zurück zum Zitat Zhao R, Yang FT, Alexander DR (2004) An oncogenic tyrosine kinase inhibits DNA repair and DNA-damage-induced Bcl-xL deamidation in T cell transformation. Cancer Cell 5:37–49CrossRefPubMed Zhao R, Yang FT, Alexander DR (2004) An oncogenic tyrosine kinase inhibits DNA repair and DNA-damage-induced Bcl-xL deamidation in T cell transformation. Cancer Cell 5:37–49CrossRefPubMed
Zurück zum Zitat Zheng X-HL, Wang N, Zhou H, Ma W-J, Zhang T-C (2015) Construction and functional analysis of luciferase reporter plasmids containing ATM and ATR gene promoters. Adv Appl Biotechnol Lect Notes Electr Eng Chapter 65:627–634 Zheng X-HL, Wang N, Zhou H, Ma W-J, Zhang T-C (2015) Construction and functional analysis of luciferase reporter plasmids containing ATM and ATR gene promoters. Adv Appl Biotechnol Lect Notes Electr Eng Chapter 65:627–634
Metadaten
Titel
IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2
verfasst von
Xiaodong Chen
Feng Chen
Yu Ren
Guobin Weng
Lijun Xu
Xiang Xue
Peter C. Keng
Soo Ok Lee
Yuhchyau Chen
Publikationsdatum
24.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02917-z

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