{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T02:31:24Z","timestamp":1726453884758},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Castration-resistant prostate cancer shows resistance to not only androgen deprivation therapy (ADT) but also X-ray therapy. On the other hand, carbon ion beams have a high biological effect and are used for various cancers showing resistance to X-ray therapy. The purposes of this study are to clarify the difference in the sensitivity of Castration-resistant prostate cancer to X-ray and carbon ion beams and to elucidate the mechanism. The androgen-insensitive prostate cancer cell line LNCaP-LA established by culturing the androgen-sensitive prostate cancer cell line LNCaP for 2\u00a0years in androgen-free medium was used for this study. First, colony formation assays were performed to investigate its sensitivity to X-ray and carbon ion beams. Next, DNA mutation analysis on 409 cancer-related genes and comprehensive transcriptome analysis (RNA-seq) were performed with a next-generation sequencer. Lethal dose 50 values of X-rays for LNCaP and LNCaP-LA were 1.4\u00a0Gy and 2.8\u00a0Gy, respectively (P\u2009&amp;lt;\u20090.01). The Lethal dose 50 values of carbon ion beams were 0.9\u00a0Gy and 0.7\u00a0Gy, respectively (P\u2009=\u20090.09). On DNA mutation analysis, AR mutation was observed specifically in LNCaP-LA. From RNA-seq, 181 genes were identified as differentially expressed genes (DEGs; FDR &amp;lt;0.10, P\u2009&amp;lt;\u20090.00076) between LNCaP and LNCaP-LA. Function analysis suggested that cell death was suppressed in LNCaP-LA, and pathway analysis suggested that the NRF2-pathway involved in intracellular oxidative stress prevention was activated in LNCaP-LA. LNCaP-LA showed X-ray resistance compared to LNCaP and sensitivity to carbon ion beams. The AR mutation and the NRF2-pathway were suggested as causes of resistance.<\/jats:p>","DOI":"10.1093\/jrr\/rrac022","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T12:28:53Z","timestamp":1650976133000},"page":"585-590","source":"Crossref","is-referenced-by-count":2,"title":["Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells"],"prefix":"10.1093","volume":"63","author":[{"given":"Mototaro","family":"Iwanaga","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidemasa","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuteru","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuji","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Oike","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Sekine","sequence":"additional","affiliation":[{"name":"Department of Urology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reika","family":"Kawabata-Iwakawa","sequence":"additional","affiliation":[{"name":"Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"},{"name":"Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"2022072201085228100_ref1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.ijrobp.2003.10.033","article-title":"External beam radiotherapy for clinically node-negative, localized hormone-refractory prostate cancer: impact of pretreatment PSA value on radiotherapeutic outcomes","volume":"59","author":"Akimoto","year":"2004","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2022072201085228100_ref2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/01.ju.0000100980.13364.a6","article-title":"10-year outcome for men with localized prostate cancer treated with external radiation therapy: results of a cohort study","volume":"171","author":"Zietman","year":"2004","journal-title":"J Urol"},{"key":"2022072201085228100_ref3","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1677\/ERC-07-0073","article-title":"The radiation response of hormone-resistant prostate cancer induced by long-term hormone therapy","volume":"14","author":"Wu","year":"2007","journal-title":"Endocr Relat Cancer"},{"key":"2022072201085228100_ref4","first-page":"1","article-title":"Particle radiotherapy with carbon ion beams","volume":"9","author":"Ohno","year":"2013","journal-title":"EPMA J"},{"key":"2022072201085228100_ref5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fonc.2016.00140","article-title":"The emerging role of carbon-ion radiotherapy","volume":"6","author":"Ebner","year":"2016","journal-title":"Front Oncol"},{"key":"2022072201085228100_ref6","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.3390\/cancers3044046","article-title":"Carbon ion radiotherapy at our institution: new facility set-up","volume":"3","author":"Ohno","year":"2011","journal-title":"Cancers"},{"key":"2022072201085228100_ref7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2022072201085228100_ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-14-350","article-title":"Image-level and group-level models for Drosophila gene expression pattern annotation","volume":"14","author":"Sun","year":"2013","journal-title":"BMC Bioinform"},{"key":"2022072201085228100_ref9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.12954\/PI.12004","article-title":"Amdrogen receptor caactivator p120 subtype beta is highly expressed in prostate cancer","volume":"1","author":"Muramatsu","year":"2013","journal-title":"Prostate Int"},{"key":"2022072201085228100_ref10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/pros.23273","article-title":"Simvastatin up-regulates annexin A10 that can inhibit the proliferation, migration, and invasion in androgen-independent human prostate cancer cells","volume":"77","author":"Miyazawa","year":"2017","journal-title":"Prostate"},{"key":"2022072201085228100_ref11","first-page":"3167","article-title":"Simvastatin in combination with meclofenamic acid migration of human prostate cancer PC-3 via an AKR1C3 mechanism","volume":"15","author":"Sekine","year":"2018","journal-title":"Oncol Lett"},{"key":"2022072201085228100_ref12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2022072201085228100_ref13","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/aja.2009.91","article-title":"The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP","volume":"12","author":"Xie","year":"2010","journal-title":"Asian J Androl"},{"key":"2022072201085228100_ref14","first-page":"137","article-title":"Androgen receptor gene mutation, rearrangement, polymorphism","volume":"2","author":"Eisermann","year":"2013","journal-title":"Transl Androl Urol"},{"key":"2022072201085228100_ref15","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1158\/2159-8290.CD-13-0679","article-title":"Androgen receptor signaling fuels DNA repair and radioresistance in prostate cancer","volume":"3","author":"Bartek","year":"2013","journal-title":"Cancer Discov"},{"key":"2022072201085228100_ref16","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/2746457","volume-title":"NRF2, a Key Regulator of Antioxidants with Two Faces towards Cancer","author":"Kim","year":"2016"},{"key":"2022072201085228100_ref17","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1042\/BST20150048","article-title":"Dysregulation of the Keap1\u2013Nrf2 pathway in cancer","volume":"43","author":"Leinonen","year":"2015","journal-title":"Biochem Soc Trans"},{"key":"2022072201085228100_ref18","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione Synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"2022072201085228100_ref19","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2 \/ HO-1 system in development, oxidative stress response and diseases : an evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"2022072201085228100_ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2015.00090","article-title":"Neuroendocrine differentiation in prostate cancer: a mechanism of radioresistance and treatment failure","volume":"5","author":"Hu","year":"2015","journal-title":"Front Oncol"},{"key":"2022072201085228100_ref21","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4149\/neo_2012_002","article-title":"Differentiation pathways in carcinogenesis and in chemo- and radioresistance","volume":"59","author":"Janikova","year":"2012","journal-title":"Neoplasma"},{"key":"2022072201085228100_ref22","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.bbamcr.2015.02.013","article-title":"Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress","volume":"1853","author":"Han","year":"2015","journal-title":"Biochim Biophys Acta"}],"container-title":["Journal of Radiation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jrr\/article-pdf\/63\/4\/585\/45023422\/rrac022.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jrr\/article-pdf\/63\/4\/585\/45023422\/rrac022.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T01:09:27Z","timestamp":1658452167000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jrr\/article\/63\/4\/585\/6589507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,20]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,5,20]]},"published-print":{"date-parts":[[2022,7,19]]}},"URL":"https:\/\/doi.org\/10.1093\/jrr\/rrac022","relation":{},"ISSN":["0449-3060","1349-9157"],"issn-type":[{"value":"0449-3060","type":"print"},{"value":"1349-9157","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,7,19]]},"published":{"date-parts":[[2022,5,20]]}}}