Radiation target and mutagenesis in intestinal tumors

肠道肿瘤的放射靶点和诱变

• 批准号: 23310036
• 负责人: KOMINAMI Ryo
• 金额: $ 12.56万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23310036/
• 关键词: 電離放射線; 発がん; 幹細胞; 大腸がん; 胸腺リンパ腫; Bcl11b; Bcl11ｂ; 放射線標的細胞; 発がん母細胞; 細胞の増殖と消失; 腸管腫瘍

Attenuated expression of Bcl11b in Lgr5-expressing intestinal crypt cells promoted regeneration of intestinal epithelial cells after the radiation-induced injury in Lgr5-Cre; Bcl11bflox/+ mice. This suggests that the origin of cells in intestinal tumors, which are enhanced by loss of one Bcl11b allele in Apcmin/+ mice, is Lgr5-expressing cells. It was also demonstrated that Bcl11b functions as a subunit of SWI/SNF chromatin remodeling complex and down-regulates transcription of Wnt/beta-catenin target genes such as c-jun. This suggests that Bcl11b impairment instigates intestinal tumor development at least in part through deregulation of beta-catenin pathway.

在表达lgr5的肠隐窝细胞中，减弱Bcl11b的表达可促进Lgr5-Cre辐射损伤后肠上皮细胞的再生；Bcl11bflox / +老鼠。这表明肠道肿瘤细胞的起源是表达lgr5的细胞，在Apcmin/+小鼠中，由于Bcl11b等位基因的缺失而增强。Bcl11b作为SWI/SNF染色质重塑复合体的一个亚基，下调Wnt/ β -catenin靶基因如c-jun的转录。这表明Bcl11b损伤至少在一定程度上是通过β -catenin通路的失调而引发肠道肿瘤的发展。

项目成果

IFN-γ–Producing and IL-17–Producing γδ T Cells Differentiate at Distinct Developmental Stages in Murine Fetal Thymus

• DOI: 10.4049/jimmunol.1302145
• 发表时间: 2014-03
• 期刊: The Journal of Immunology
• 作者: K. Shibata;H. Yamada;Masataka Nakamura;S. Hatano;Y. Katsuragi;R. Kominami;Y. Yoshikai

Cell of origin in radiation-induced premalignant thymocytes in mice conditionally losing one Bcl11b allele

条件性丢失一个 Bcl11b 等位基因的小鼠中辐射诱导的癌前胸腺细胞的起源细胞

• 发表时间: 2013
• 期刊: Cancer Sci
• 影响因子: 5.7
• 作者: Go R;Hirose S;Katsuragi Y;Obata M;Abe M;Mishima Y;Sakimura K;Kominami R
• 通讯作者: Kominami R

Bcl11b transcription factor plays a role in the maintenance of the ameloblast-progenitors in mouse adult maxillary incisors

• DOI: 10.1016/j.mod.2013.05.002
• 发表时间: 2013-09-01
• 期刊: MECHANISMS OF DEVELOPMENT
• 影响因子: 2.6
• 作者: Katsuragi, Yoshinori;Anraku, Junko;Kominami, Ryo
• 通讯作者: Kominami, Ryo

Epigenetic Thpok silencing limits the time window to choose CD4+ helper-lineage fate in the thymus

• DOI: 10.1038/emboj.2013.47
• 发表时间: 2013-04-17
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Tanaka, Hirokazu;Naito, Taku;Taniuchi, Ichiro
• 通讯作者: Taniuchi, Ichiro

Compound Heterozygosity of the Functionally Null Cdh23v-ngt and Hypomorphic Cdh23ahl/i Alleles Leads to Early-onset Progressive Hearing Loss in Mice

功能性无效 Cdh23v-ngt 和亚形 Cdh23ahl/i 等位基因的复合杂合性导致小鼠早发进行性听力损失

• 发表时间: 2013
• 期刊: Exp Anim
• 作者: Miyasaka Y;Suzuki S;Ohshiba Y;Watanabe K;Sagara Y;Yasuda SP;Matsuoka K;Shitara H;Yonekawa H;Kominami R;Kikkawa Y
• 通讯作者: Kikkawa Y