WEKO3
アイテム
Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis
https://repo.qst.go.jp/records/46596
https://repo.qst.go.jp/records/4659676e1a678-7efc-4458-9828-cb2063ee83e8
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-09-18 | |||||
| タイトル | ||||||
| タイトル | Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Daino, Kazuhiro
× Daino, Kazuhiro× Imaoka, Tatsuhiko× Morioka, Takamitsu× Tani, Shusuke× Iizuka, Daisuke× Nishimura, Mayumi× Shimada, Yoshiya× 臺野 和広× 今岡 達彦× 森岡 孝満× 谷 修祐× 飯塚 大輔× 西村 まゆみ× 島田 義也 |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A cells by shRNA-mediated RNA interference and examined its effect in a three-dimensional culture model. Genome-wide gene expression profiling by microarray and quantitative RT-PCR were performed to identify alterations in gene expression in BRIP1-knockdown cells compared with control cells. The microarray data were further investigated using the pathway analysis and Gene Set Enrichment Analysis (GSEA) for pathway identification. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1, RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with control cells were categorized into several functional groups, such as cell adhesion, polarity, growth, signal transduction, and developmental process. Signaling-pathway analyses showed dysregulation of multiple cellular signaling pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary morphogenesis and causes neoplastic-like changes, possibly via dysregulating multiple cellular signaling pathways functioning in the normal development of mammary glands. | |||||
| 書誌情報 |
PLoS ONE (Online only:URL:http://www.plosone.org) 巻 8, 号 9, p. e74013, 発行日 2013-09 |
|||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1932-6203 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1371/journal.pone.0074013 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074013 | |||||
| 関連名称 | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074013 | |||||
