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- Title
Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway.
- Authors
Akira Sakamaki; Yoshinori Katsuragi; Kensuke Otsuka; Masanori Tomita; Miki Obata; Tomohiro Iwasaki; Manabu Abe; Toshihiro Sato; Masako Ochiai; Yoshiyuki Sakuraba; Yutaka Aoyagi; Yoichi Gondo; Kenji Sakimura; Hitoshi Nakagama; Yukio Mishima; Ryo Kominami
- Abstract
SWI/SNF chromatin remodeling complexes constitute a highly related family of multi-subunit complexes to modulate transcription, and SWI/SNF subunit genes are collectively mutated in 20% of all human cancers. Bcl11b is a SWI/SNF subunit and acts as a haploinsufficient tumor suppressor in leukemia/lymphomas. Here, we show expression of Bcl11b in intestinal crypt cells and promotion of intestinal tumorigenesis by Bcl11b attenuation in Apcmin/+ mice. Of importance, mutations or allelic loss of BCL11B was detected in one-third of human colon cancers. We also show that attenuated Bcl11b activity in the crypt base columnar (CBC) cells expressing the Lgr5 stem cell marker enhanced regeneration of intestinal epithelial cells after the radiation-induced injury. Interestingly, BCL11B introduction in human cell lines downregulated transcription of β-catenin target genes, whereas Bcl11b attenuation in Lgr5+ CBCs increased expression of β-catenin targets including c-Myc and cyclin D1. Together, our results argue that Bcl11b impairment promotes tumor development in mouse and human intestine at least in part through deregulation of β-catenin pathway.
- Publication
Carcinogenesis, 2015, Vol 36, Issue 6, p622
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgv044