Bcl11b heterozygosity provides intestinal tumor susceptibility and increased regeneration capacity after gamma-irradiation

Abstract

Bcl11b tumor suppressor is expressed in CBC cells and transit amplifying (TA) cells of the crypt in small intestine. When Bcl11b^KO/+ genotype was introduced to Apc^min/+ mice, adenoma incidence was about twice increased. We thus examined radiation effect on adenoma incidence. The incidence was increased at 16 weeks after 3 Gy irradiation and the increased level was significantly higher in Bcl11b^KO/+ mice than in Bcl11b^+/+ mice. We next examined cell proliferation and apoptosis of Bcl11b expressing intestinal cells in mice that were subjected to whole-body gamma-irradiation (12 Gy). Differences were detected at 24 h after, a time when morphological change occurred; the crypt region of small intestine was elongated and the number of Ki67-positive cells in crypt increased in Bcl11b^KO/+ mice relative to Bcl11b^+/+ mice. On the other hand, Bcl11b-positive cells and apoptotic cells decreased. As for intestine at 96 h after, crypt regeneration was noted, and the regeneration level was more marked in Bcl11b^KO/+ mice, together with the increased number of Ki67-positive cells. These results indicate a higher capacity of Bcl11b^KO/+ crypt cells in small intestine to regenerate after damage. This may reflect a decrease in the cell-proliferation suppressive activity of Bcl11b.