Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.

O.J. Sansom; K.R. Reed; M.van de Wetering; V. Muncan; D. Winston; J.C. Clevers; A.R. Clarke

Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.

O.J. Sansom, K.R. Reed, M.van de Wetering, V. Muncan, D. Winston, J.C. Clevers, A.R. Clarke

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

Abstract

Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions developing 20 days after Apc loss. In these circumstances, all adenomas (but not smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we analyzed whether cyclin D1 deficiency affected adenoma formation 20 days following induced loss of Apc. Unlike AhCre(+) Apc(fl/fl) mice (which all developed adenomas), doubly mutant AhCre(+) Apc(fl/fl) cyclin D1(-/-) mice only developed small lesions. Taken together, this argues that cyclin D1up-regulation in intestinal neoplasia is important for tumor progression rather than initiation.

Original language	English
Pages (from-to)	28463-28467
Journal	The Journal of biological chemistry
Volume	280
Publication status	Published - 2005

Cite this

@article{8344e08fbc68405298653f2db590e32e,

title = "Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.",

abstract = "Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions developing 20 days after Apc loss. In these circumstances, all adenomas (but not smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we analyzed whether cyclin D1 deficiency affected adenoma formation 20 days following induced loss of Apc. Unlike AhCre(+) Apc(fl/fl) mice (which all developed adenomas), doubly mutant AhCre(+) Apc(fl/fl) cyclin D1(-/-) mice only developed small lesions. Taken together, this argues that cyclin D1up-regulation in intestinal neoplasia is important for tumor progression rather than initiation.",

author = "O.J. Sansom and K.R. Reed and Wetering, {M.van de} and V. Muncan and D. Winston and J.C. Clevers and A.R. Clarke",

note = "doi: 10.1074/jbc.M500191200",

year = "2005",

language = "English",

volume = "280",

pages = "28463--28467",

journal = "The Journal of biological chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

}

TY - JOUR

T1 - Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.

AU - Sansom, O.J.

AU - Reed, K.R.

AU - Wetering, M.van de

AU - Muncan, V.

AU - Winston, D.

AU - Clevers, J.C.

AU - Clarke, A.R.

N1 - doi: 10.1074/jbc.M500191200

PY - 2005

Y1 - 2005

N2 - Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions developing 20 days after Apc loss. In these circumstances, all adenomas (but not smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we analyzed whether cyclin D1 deficiency affected adenoma formation 20 days following induced loss of Apc. Unlike AhCre(+) Apc(fl/fl) mice (which all developed adenomas), doubly mutant AhCre(+) Apc(fl/fl) cyclin D1(-/-) mice only developed small lesions. Taken together, this argues that cyclin D1up-regulation in intestinal neoplasia is important for tumor progression rather than initiation.

AB - Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical for intestinal adenoma development. We show here that, unlike cyclin D1 reporter assays, endogenous cyclin D1 levels are not affected following antagonism of the Wnt pathway in vitro, nor is cyclin D1immediately up-regulated following conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a delayed manner in a small subset of cells, suggesting such up-regulation occurs as a secondary event. We also analyzed the immediate consequences of Apc loss in a cyclin D1(-/-) background and failed to find any cyclin D1-dependent phenotypes. However, we did observe elevated cyclin D1 expression in lesions developing 20 days after Apc loss. In these circumstances, all adenomas (but not smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we analyzed whether cyclin D1 deficiency affected adenoma formation 20 days following induced loss of Apc. Unlike AhCre(+) Apc(fl/fl) mice (which all developed adenomas), doubly mutant AhCre(+) Apc(fl/fl) cyclin D1(-/-) mice only developed small lesions. Taken together, this argues that cyclin D1up-regulation in intestinal neoplasia is important for tumor progression rather than initiation.

M3 - Article

SN - 0021-9258

VL - 280

SP - 28463

EP - 28467

JO - The Journal of biological chemistry

JF - The Journal of biological chemistry

ER -

Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine.

Abstract

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