Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells
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 clari...
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| Veröffentlicht in: | Journal of radiation research 2022-07, Vol.63 (4), p.585-590 |
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| creator | Iwanaga, Mototaro Kawamura, Hidemasa Kubo, Nobuteru Mizukami, Tatsuji Oike, Takahiro Sato, Hiro Miyazawa, Yoshiyuki Sekine, Yoshitaka Kawabata-Iwakawa, Reika Nishiyama, Masahiko Ohno, Tatsuya Nakano, Takashi |
| description | 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 years 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 Gy and 2.8 Gy, respectively (P |
| doi_str_mv | 10.1093/jrr/rrac022 |
| format | Article |
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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 years 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 Gy and 2.8 Gy, respectively (P < 0.01). The Lethal dose 50 values of carbon ion beams were 0.9 Gy and 0.7 Gy, respectively (P = 0.09). 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 <0.10, P < 0.00076) 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.</description><identifier>ISSN: 0449-3060</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1093/jrr/rrac022</identifier><identifier>PMID: 35589101</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Analysis ; Androgens ; Cell death ; Development and progression ; Fundamental Radiation Science ; Gene mutations ; Genes ; Prostate cancer ; RNA</subject><ispartof>Journal of radiation research, 2022-07, Vol.63 (4), p.585-590</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-f8dcbcd3bd510d916946bb2c3b2d786a4312181afbebe039aa61ecbcc2c54d33</citedby><cites>FETCH-LOGICAL-c569t-f8dcbcd3bd510d916946bb2c3b2d786a4312181afbebe039aa61ecbcc2c54d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303586/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303586/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35589101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwanaga, Mototaro</creatorcontrib><creatorcontrib>Kawamura, Hidemasa</creatorcontrib><creatorcontrib>Kubo, Nobuteru</creatorcontrib><creatorcontrib>Mizukami, Tatsuji</creatorcontrib><creatorcontrib>Oike, Takahiro</creatorcontrib><creatorcontrib>Sato, Hiro</creatorcontrib><creatorcontrib>Miyazawa, Yoshiyuki</creatorcontrib><creatorcontrib>Sekine, Yoshitaka</creatorcontrib><creatorcontrib>Kawabata-Iwakawa, Reika</creatorcontrib><creatorcontrib>Nishiyama, Masahiko</creatorcontrib><creatorcontrib>Ohno, Tatsuya</creatorcontrib><creatorcontrib>Nakano, Takashi</creatorcontrib><title>Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells</title><title>Journal of radiation research</title><addtitle>J Radiat Res</addtitle><description>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 years 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 Gy and 2.8 Gy, respectively (P < 0.01). The Lethal dose 50 values of carbon ion beams were 0.9 Gy and 0.7 Gy, respectively (P = 0.09). 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 <0.10, P < 0.00076) 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.</description><subject>Analysis</subject><subject>Androgens</subject><subject>Cell death</subject><subject>Development and progression</subject><subject>Fundamental Radiation Science</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Prostate cancer</subject><subject>RNA</subject><issn>0449-3060</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNp9kctr3DAQxkVpaLZJT70XQ6EUghM9bNm6FELaPCCQyx5yE6OHUwWvtJHswv73nWW3oYEQdNAw85uPmfkI-czoKaNKnD3mfJYzWMr5O7JgolG1Ym33nixog7Ggkh6Sj6U8Uso72tIP5FC0ba8YZQuy_JlmM_p6hI3PVVoFWyqIMG5KKFUaKgtlyjCFFGvMu-q-zrCps8fyBHGq1jlhMHkEo0UF68exHJODAcbiP-3_I7K8_LW8uK5v765uLs5va9tKNdVD76yxThjXMuoUk6qRxnArDHddL6ERjLOewWC88VQoAMk8dlhu28YJcUR-7GTXs1l5Z33EUUe9zmEFeaMTBP2yEsNv_ZD-aCWoaHuJAt_3Ajk9zb5MehXKdgOIPs1Fcym7TvGuoYh-3aEPMHod4pBQ0W5xfd5JxRjnvEHq9BUKn_N42RT9EDD_ouFk12DxjiX74Xl6RvXWXY3u6r27SH_5f-Fn9p-dCHzbAWlev6n0F_H0r9Q</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Iwanaga, Mototaro</creator><creator>Kawamura, Hidemasa</creator><creator>Kubo, Nobuteru</creator><creator>Mizukami, Tatsuji</creator><creator>Oike, Takahiro</creator><creator>Sato, Hiro</creator><creator>Miyazawa, Yoshiyuki</creator><creator>Sekine, Yoshitaka</creator><creator>Kawabata-Iwakawa, Reika</creator><creator>Nishiyama, Masahiko</creator><creator>Ohno, Tatsuya</creator><creator>Nakano, Takashi</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220701</creationdate><title>Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells</title><author>Iwanaga, Mototaro ; Kawamura, Hidemasa ; Kubo, Nobuteru ; Mizukami, Tatsuji ; Oike, Takahiro ; Sato, Hiro ; Miyazawa, Yoshiyuki ; Sekine, Yoshitaka ; Kawabata-Iwakawa, Reika ; Nishiyama, Masahiko ; Ohno, Tatsuya ; Nakano, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-f8dcbcd3bd510d916946bb2c3b2d786a4312181afbebe039aa61ecbcc2c54d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Analysis</topic><topic>Androgens</topic><topic>Cell death</topic><topic>Development and progression</topic><topic>Fundamental Radiation Science</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Prostate cancer</topic><topic>RNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwanaga, Mototaro</creatorcontrib><creatorcontrib>Kawamura, Hidemasa</creatorcontrib><creatorcontrib>Kubo, Nobuteru</creatorcontrib><creatorcontrib>Mizukami, Tatsuji</creatorcontrib><creatorcontrib>Oike, Takahiro</creatorcontrib><creatorcontrib>Sato, Hiro</creatorcontrib><creatorcontrib>Miyazawa, Yoshiyuki</creatorcontrib><creatorcontrib>Sekine, Yoshitaka</creatorcontrib><creatorcontrib>Kawabata-Iwakawa, Reika</creatorcontrib><creatorcontrib>Nishiyama, Masahiko</creatorcontrib><creatorcontrib>Ohno, Tatsuya</creatorcontrib><creatorcontrib>Nakano, Takashi</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwanaga, Mototaro</au><au>Kawamura, Hidemasa</au><au>Kubo, Nobuteru</au><au>Mizukami, Tatsuji</au><au>Oike, Takahiro</au><au>Sato, Hiro</au><au>Miyazawa, Yoshiyuki</au><au>Sekine, Yoshitaka</au><au>Kawabata-Iwakawa, Reika</au><au>Nishiyama, Masahiko</au><au>Ohno, Tatsuya</au><au>Nakano, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells</atitle><jtitle>Journal of radiation research</jtitle><addtitle>J Radiat Res</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>63</volume><issue>4</issue><spage>585</spage><epage>590</epage><pages>585-590</pages><issn>0449-3060</issn><eissn>1349-9157</eissn><abstract>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 years 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 Gy and 2.8 Gy, respectively (P < 0.01). The Lethal dose 50 values of carbon ion beams were 0.9 Gy and 0.7 Gy, respectively (P = 0.09). 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 <0.10, P < 0.00076) 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.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35589101</pmid><doi>10.1093/jrr/rrac022</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Androgens Cell death Development and progression Fundamental Radiation Science Gene mutations Genes Prostate cancer RNA |
| title | Double-layer omics analysis of castration- and X-ray-resistant prostate cancer cells |
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