Id2 deletion attenuates Apc-deficient ileal tumor formation

The expression level of inhibitor of DNA binding 2 (Id2) is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promote...

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Main Authors:	Biyajima, Kyoko, Kakizaki, Fumihiko, Shen, Xiaodong, Mori, Kentaro, Sugai, Manabu, Taketo, M. Mark, Yokota, Yoshifumi
Format:	Online
Language:	English
Published:	The Company of Biologists 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542283/

id	pubmed-4542283
recordtype	oai_dc
spelling	pubmed-45422832015-09-16 Id2 deletion attenuates Apc-deficient ileal tumor formation Biyajima, Kyoko Kakizaki, Fumihiko Shen, Xiaodong Mori, Kentaro Sugai, Manabu Taketo, M. Mark Yokota, Yoshifumi Research Article The expression level of inhibitor of DNA binding 2 (Id2) is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1), known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of ApcΔ716 mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in ApcΔ716 mice. The Company of Biologists 2015-07-10 /pmc/articles/PMC4542283/ /pubmed/26163528 http://dx.doi.org/10.1242/bio.012252 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Biyajima, Kyoko Kakizaki, Fumihiko Shen, Xiaodong Mori, Kentaro Sugai, Manabu Taketo, M. Mark Yokota, Yoshifumi
spellingShingle	Biyajima, Kyoko Kakizaki, Fumihiko Shen, Xiaodong Mori, Kentaro Sugai, Manabu Taketo, M. Mark Yokota, Yoshifumi Id2 deletion attenuates Apc-deficient ileal tumor formation
author_facet	Biyajima, Kyoko Kakizaki, Fumihiko Shen, Xiaodong Mori, Kentaro Sugai, Manabu Taketo, M. Mark Yokota, Yoshifumi
author_sort	Biyajima, Kyoko
title	Id2 deletion attenuates Apc-deficient ileal tumor formation
title_short	Id2 deletion attenuates Apc-deficient ileal tumor formation
title_full	Id2 deletion attenuates Apc-deficient ileal tumor formation
title_fullStr	Id2 deletion attenuates Apc-deficient ileal tumor formation
title_full_unstemmed	Id2 deletion attenuates Apc-deficient ileal tumor formation
title_sort	id2 deletion attenuates apc-deficient ileal tumor formation
description	The expression level of inhibitor of DNA binding 2 (Id2) is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716) mice. Genetic depletion of Id2 in ApcΔ716 mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1), known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of ApcΔ716 mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in ApcΔ716 mice.
publisher	The Company of Biologists
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542283/
_version_	1613261634332000256

Id2 deletion attenuates Apc-deficient ileal tumor formation

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