{"created":"2023-06-19T10:29:31.879113+00:00","id":1637,"links":{},"metadata":{"_buckets":{"deposit":"54a097f7-d9e9-4e93-83a2-ecec7e3e3114"},"_deposit":{"created_by":31,"id":"1637","owners":[31],"pid":{"revision_id":0,"type":"depid","value":"1637"},"status":"published"},"_oai":{"id":"oai:kwmed.repo.nii.ac.jp:00001637","sets":["1709617079800:35:307:556"]},"author_link":[],"item_1694495855422":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_type":"VoR"}]},"item_3_biblio_info_12":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"79","bibliographicPageStart":"65","bibliographicVolumeNumber":"39","bibliographic_titles":[{"bibliographic_title":"川崎医学会誌","bibliographic_titleLang":"ja"},{"bibliographic_title":"Kawasaki medical journal","bibliographic_titleLang":"en"}]}]},"item_3_description_8":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_description":"原著","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_identifier_14":{"attribute_name":"URL","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"http://igakkai.kms-igakkai.com/wp/wp-content/uploads/2013/KMJ39(3)65-79.2013.pdf"}]},"item_3_relation_20":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.11482/2013/KMJ39(3)65-79.2013.pdf","subitem_relation_type_select":"DOI"}}]},"item_3_source_id_1":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AN00045593","subitem_source_identifier_type":"NCID"},{"subitem_source_identifier":"AN12940574","subitem_source_identifier_type":"NCID"}]},"item_3_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0386-5924","subitem_source_identifier_type":"PISSN"},{"subitem_source_identifier":"2758-089X","subitem_source_identifier_type":"EISSN"}]},"item_3_text_6":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学乳腺甲状腺外科学"},{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学乳腺甲状腺外科学"},{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学病理学"},{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学乳腺甲状腺外科学"},{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学病理学"},{"subitem_text_language":"ja","subitem_text_value":"川崎医科大学乳腺甲状腺外科学"}]},"item_3_text_7":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Department of Breast and Thyroid Surgery, Kawasaki Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Breast and Thyroid Surgery, Kawasaki Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Pathology 2, Kawasaki Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Breast and Thyroid Surgery, Kawasaki Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Pathology 2, Kawasaki Medical School"},{"subitem_text_language":"en","subitem_text_value":"Department of Breast and Thyroid Surgery, Kawasaki Medical School"}]},"item_3_textarea_10":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"乳癌を含め多くの固形腫瘍において,癌幹細胞(CSC)が治療抵抗性や再発の原因となることが示唆されている.一方, エストロゲン感受性乳癌におけるCSCの制御機構に関する研究は少ない.そこで,エストロゲン受容体(ER)陽性乳癌細胞におけるエストロゲンや抗エストロゲン薬(抗E薬)の細胞増殖やCSC制御に与える影響について検討した.さらに,内分泌療法抵抗性乳癌に有効性が期待されているmTOR阻害薬エベロリムス(EVE)と抗E薬との併用効果も検討した.ER陽性乳癌の実験モデルとして,エストロゲン高感受性(HS)のMCF-7,T-47D乳癌細胞株,エストロゲン低感受性(LS)のKPL-1,KPL-3C乳癌細胞株を用いた.薬剤は,17β-estradiol(E2),4-hydroxytamoxifen(4-OHT),fulvestrant(FUL),EVEを用い,細胞増殖,細胞周期,アポトーシス,CSC比率に与える影響を検討した.CSCの同定には,CD44/CD24/EpCAM抗体を用いたフローサイトメトリー法及びmammosphere assayを用いた.ER-α,PgRおよびER関連転写因子(GATA3等)の発現は免疫細胞化学的に検討した.結果として(1)LS細胞株では,PgRの発現が認められなかった.それ以外のER関連因子は,HS細胞株,LS細胞株ともに高発現が認められた.(2)HS細胞株はLS細胞株に比べ,E2による細胞増殖の促進効果,CSC比率の増加効果が,ともにより顕著であった.(3)HS細胞株はLS細胞株に比べ,抗E薬による細胞増殖の抑制効果,CSC比率の低下効果がより顕著であった.(4)EVEと抗E薬の併用は,LS細胞株において相加的な細胞増殖抑制効果を示した.両薬の併用により,一部の細胞株ではCSC比率の減少効果が増強された.以上の結果は,LS乳癌において,抗E薬の増殖抑制効果ばかりでなく,CSC比率の低下効果も減弱していることを示唆している.抗E薬抵抗性獲得のメカニズムの一つとして,CSC制御機構の異常が関わっている可能性がある.また,一部の乳癌細胞株において,抗E薬とEVE併用の結果から,内分泌抵抗性乳癌におけるEVEの有用性が示唆された."}]},"item_3_textarea_11":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_textarea_language":"en","subitem_textarea_value":"Recent studies have revealed the existence of cancer stem cells (CSCs) in breast cancer. CSCs may play critical roles in resistance to anticancer agents and radiation, and in the development of metastases. However, the roles of CSCs in estrogen-responsive breast cancer remain to be elucidated. In this study, we investigated the effects of estrogen and antiestrogens (AEs) as well as an inhibitor of mammalian target of rapamycin (mTOR), everolimus (EVE) on the cell growth and regulation of the CSC population in estrogen-responsive breast cancer cell lines (BCCLs). Two high estrogen-sensitivity (HS) BCCLs, MCF-7 and T-47D, and two low estrogen-sensitivity (LS) BCCLs, KPL-1 and KPL-3C, were used. 4-hydroxytamoxifen (4-OHT) and a steroidal AE fulvestrant (FUL) and EVE were studied. Expression levels of ER-related proteins, ER-α, progesterone receptor (PgR), GATA3, FOXA1 and XBP1 were immunocytochemically investigated. The effects of the agents on the cell growth, cell cycle progression, apoptosis and regulation of the CSC population, defined as EpCAM-positive, CD44-high, CD24-low or negative cells using flow cytometery or mammosphere assay, were examined. Experimental results are as follows: (1) The LS BCCLs were negative for PgR but positive for the other ER-related proteins examined. The HS BCCLs were positive for all the ER-related proteins. The LS BCCLs were tumorigenic in female nude mice without estrogen supplementation, but the HS BCCLs were not. (2) The increase in cell growth induced by 17β-estradiol (E2) was more pronounced in the HS BCCLs. The decrease in cell growth induced by 4-OHT or FUL was more pronounced in the HS BCCLs. The AEs inhibited the G1-S cell cycle progression and induced a slight apoptosis. (3) E2 significantly increased the proportion of CSCs in all the cell lines tested. The increase in the CSC proportion by E2 was more pronounced in the HS BCCLs. The decrease in the CSC proportion by both 4-OHT and FUL was more pronounced in the HS BCCLs. (4) The decrease in the cell growth by EVE was more pronounced in LS BCCLs. Combined treatment of 4-OHT or FUL with EVE showed an additive effect in the LS BCCLs but not in the HS BCCLs. (5) Although EVE alone slightly increased the proportion of CSCs, the combined treatment of 4-OHT or FUL with EVE did not increased it. In conclusions, the HS BCCLs were more sensitive to estrogen and AEs than the LS BCCLs with regard to the cell growth response and CSC regulation. Thus, the LS BCCLs were more resistant to AE. It should be noted that EVE was more active in the LS BCCLs. These findings suggest that the combined use of EVE with AEs may be more useful in patients with breast cancer resistant to AEs."}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山下, 哲正","creatorNameLang":"ja"},{"creatorName":"ヤマシタ, テツマサ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"紅林, 淳一","creatorNameLang":"ja"},{"creatorName":"クレバヤシ, ジュンイチ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"鹿股, 直樹","creatorNameLang":"ja"},{"creatorName":"カノマタ, ナオキ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"下, 登志朗","creatorNameLang":"ja"},{"creatorName":"シモ, トシロウ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"森谷, 卓也","creatorNameLang":"ja"},{"creatorName":"モリヤ, タクヤ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"園尾, 博司","creatorNameLang":"ja"},{"creatorName":"ソノオ, ヒロシ","creatorNameLang":"ja-Kana"}]},{"creatorNames":[{"creatorName":"Yamashita, Tetsumasa","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Kurebayashi, Junichi","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Kanomata, Naoki","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Shimo, Toshiro","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Moriya, Takuya","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Sonoo, Hiroshi","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-02-21"}],"displaytype":"detail","filename":"KMJ39(3)65-79.2013.pdf","filesize":[{"value":"862.4 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"PDF","objectType":"fulltext","url":"https://kwmed.repo.nii.ac.jp/record/1637/files/KMJ39(3)65-79.2013.pdf"},"version_id":"150e7911-d40d-42c8-9d23-9fdb65f564df"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"乳癌","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"癌幹細胞","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"エストロゲン受容体","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"抗エストロゲン薬","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"エベロリムス","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"Breast cancer stem cell","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"antiestrogen","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"everolimus","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"エストロゲン受容体陽性乳癌細胞における抗エストロゲン薬とmTOR阻害薬エベロリムスの細胞増殖及び癌幹細胞制御に対する効果","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"エストロゲン受容体陽性乳癌細胞における抗エストロゲン薬とmTOR阻害薬エベロリムスの細胞増殖及び癌幹細胞制御に対する効果","subitem_title_language":"ja"},{"subitem_title":"Effects of antiestrogens and an mTOR inhibitor everolimus on the cell growth and regulation of cancer stem population in estrogen receptor-positive breast cancer cells","subitem_title_language":"en"}]},"item_type_id":"3","owner":"31","path":["556"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2017-01-23"},"publish_date":"2017-01-23","publish_status":"0","recid":"1637","relation_version_is_last":true,"title":["エストロゲン受容体陽性乳癌細胞における抗エストロゲン薬とmTOR阻害薬エベロリムスの細胞増殖及び癌幹細胞制御に対する効果"],"weko_creator_id":"31","weko_shared_id":-1},"updated":"2023-10-11T04:46:32.286496+00:00"}