{"created":"2025-03-01T12:16:16.209992+00:00","id":2027571,"links":{},"metadata":{"_buckets":{"deposit":"9c238a73-dcfd-4731-8bc6-f92da6e780c3"},"_deposit":{"created_by":41,"id":"2027571","owner":"41","owners":[41],"pid":{"revision_id":0,"type":"depid","value":"2027571"},"status":"published"},"_oai":{"id":"oai:hiroshima.repo.nii.ac.jp:02027571","sets":["1727147343679:1730443989164:1730444012901"]},"author_link":[],"item_1617186331708":{"attribute_name":"Title","attribute_value_mlt":[{"subitem_title":"ポリコーム遺伝子群mel-18のハプロインサフィシエンシーによるマウスの腫瘍原生獲得機構の解析 <原著>","subitem_title_language":"ja"},{"subitem_title":"mel-18,a Polycomb Group Gene, is Haploinsufficient for Murine Spontaneous Adenocarcinoma","subitem_title_language":"en"}]},"item_1617186419668":{"attribute_name":"Creator","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"木村, まり","creatorNameLang":"ja"},{"creatorName":"Kimura, Mari","creatorNameLang":"en"}],"familyNames":[{"familyName":"木村","familyNameLang":"ja"},{"familyName":"Kimura","familyNameLang":"en"}],"givenNames":[{"givenName":"まり","givenNameLang":"ja"},{"givenName":"Mari","givenNameLang":"en"}]}]},"item_1617186476635":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_1617186609386":{"attribute_name":"Subject","attribute_value_mlt":[{"subitem_subject":"ポリコーム遺伝子群","subitem_subject_scheme":"Other"},{"subitem_subject":"mel-18","subitem_subject_scheme":"Other"},{"subitem_subject":"遺伝子改変マウス","subitem_subject_scheme":"Other"},{"subitem_subject":"ハプロインサフィシエンシー","subitem_subject_scheme":"Other"},{"subitem_subject":"発癌","subitem_subject_scheme":"Other"},{"subitem_subject":"Polycomb group genes","subitem_subject_scheme":"Other"},{"subitem_subject":"haploinsufficiency","subitem_subject_scheme":"Other"},{"subitem_subject":"490","subitem_subject_scheme":"NDC"}]},"item_1617186626617":{"attribute_name":"Description","attribute_value_mlt":[{"subitem_description":"The Polycomb group (PcG) gene products form protein complexes in mammalian cell nuclei and maintain chromatin silencing of target genes. mel-18,a mammalian PcG homologue, is considered to regulate cell cycle progression, cell death, or senescence based on the findings obtained from its knockout mice. Mel-18 participates in Polycomb protein complexes and the immunohistochemical analyses have shown that Mel-18 is located in the nucleus as a speckled distribution. Recently, mel-18 hemizygous mice have shown to develop adenocarcinomas, most of which were classified as breast cancers. Although no gross rearrangements or nucleotide mutations in the remaining mel-18 allele despite of the expression of Mel-18 protein in mel-18 hemizygous mice, we found that, in mel-18 hemizygous mice, a pattern of protein complexes including Mel-18 was destructed, and that a distribution pattern of Mel-18 changed to a micro-speckled pattern. In addition, murine mammary gland cells expressing reduced level of Mel-18 by antisense introduction acquired tumorigenicity and also showed an altered distribution of Mel-18 in the nucleus similar to those observed in tumor cells of mel-18 hemizygous mice. Examinations of the expression of other breast cancer-associated genes demonstrated that brca1 expression was reduced, whereas tbx2 expression was induced both in the mel-18 hemizygous tumor cells and mel-18 antisense-introduced cells. These results strongly suggest that mel-18 is a novel murine tumor suppressor gene and its haploinsufficiency results in tumorigenesis, possibly due to disruption of the protein complex formation and failure in silencing of target genes.","subitem_description_language":"en"},{"subitem_description":"ポリコーム遺伝子群は, ショウジョウバエでホメオボックス遺伝子群の負の制御因子として同定された。その遺伝子産物は核内でタンパク質複合体を形成し, 標的遺伝子の転写が抑制されるヘテロクロマチンの維持(クロマチンサイレンシング)に寄与している。哺乳類ホモログのmel-18のノックアウトマウスは, 体の前後軸形成異常, リンパ球の細胞周期異常による重篤な免疫不全を呈した。mel-18は細胞死も制御しており, 細胞周期, 細胞死双方への関与より, 癌との関連が予想された。mel-18発現の低下したNIH3T3細胞は腫瘍形質を獲得し, in vitroでは癌抑制の活性が確認されたが, mel-18欠損マウスは生後3～4週間で死亡するため, 生体レベルでの証明は不可能であった。近年mel-18へテロ接合性マウスに乳癌を中心とする腺癌の発生が認められた。腫瘍の残存mel-18遺伝子座には, 変異, 欠失は認められなかった。Mel-18タンパク質は核内で他のポリコームタンパク質等と複合体を形成するが, mel-18^<+/->マウスの臓器ではこの複合体が消失していた。抗Mel-18抗体を用いた蛍光免疫染色では, 野生型細胞では核内に十数個の粗大な顆粒状の構造物がみられ, これがMel-18を含むポリコームタンパク質複合体の一部ではないかと考えられた。mel-18へテロ接合性マウスの腫瘍細胞ではこの破砕像が観察された。正常マウス乳腺細胞にmel-18アンチセンスを導入すると, 高率に腫瘍を形成し, 核内のMel-18タンパク質局在は, mel-18^<+/->マウスの腫瘍細胞と同様の破砕パターンを呈した。他の乳癌関連遺伝子の検索では, mel-18の発現量の少ない細胞で癌抑制遺伝子のbrca1の発現が減少, 癌遺伝子のtbx2の発現が増加しており, これらがmel-18の標的遺伝子であることが示唆された。以上より, mel-18のハプロインサフィシエンシーは, Mel-18複合体を不安定化し, 標的遺伝子のへテロクロマチン領域の破綻により腫瘍原生獲得に至ったものと考えられた。","subitem_description_language":"ja"}]},"item_1617186643794":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"広島大学医学出版会"}]},"item_1617186660861":{"attribute_name":"Date","attribute_value_mlt":[{"subitem_date_issued_datetime":"2006-03-21","subitem_date_issued_type":"Created"}]},"item_1617186702042":{"attribute_name":"Language","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_1617186819068":{"attribute_name":"identifier_registration","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15027/616","subitem_identifier_reg_type":"JaLC"}]},"item_1617186920753":{"attribute_name":"Source Identifier","attribute_value_mlt":[{"subitem_source_identifier":"0018-2087","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AN00213202","subitem_source_identifier_type":"NCID"}]},"item_1617187024783":{"attribute_name":"開始ページ","attribute_value_mlt":[{"subitem_start_page":"53"}]},"item_1617187056579":{"attribute_name":"bibliographic_information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2002-02-28","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"62","bibliographicPageStart":"53","bibliographicVolumeNumber":"50","bibliographic_titles":[{"bibliographic_title":"広島大学医学雑誌"},{"bibliographic_title":"Medical journal of Hiroshima Universtiy"}]}]},"item_1617258105262":{"attribute_name":"item_1617258105262","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_1617265215918":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1617349709064":{"attribute_name":"Contributor","attribute_value_mlt":[{"contributorNames":[{"contributorName":"国立情報学研究所"}]}]},"item_1617605131499":{"attribute_name":"File","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2006-03-21"}],"displaytype":"simple","filename":"KJ00000146133.pdf","filesize":[{"value":"797.1 KB"}],"mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://hiroshima.repo.nii.ac.jp/record/2027571/files/KJ00000146133.pdf"},"version_id":"ce29d027-2a9f-4953-a830-97b506f24b92"}]},"item_1732771732025":{"attribute_name":"旧ID","attribute_value":"616"},"item_title":"ポリコーム遺伝子群mel-18のハプロインサフィシエンシーによるマウスの腫瘍原生獲得機構の解析 <原著>","item_type_id":"40003","owner":"41","path":["1730444012901"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2006-03-21"},"publish_date":"2006-03-21","publish_status":"0","recid":"2027571","relation_version_is_last":true,"title":["ポリコーム遺伝子群mel-18のハプロインサフィシエンシーによるマウスの腫瘍原生獲得機構の解析 <原著>"],"weko_creator_id":"41","weko_shared_id":-1},"updated":"2025-03-01T12:16:30.511537+00:00"}