Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice

James Hulit, Chenguang Wang, Zhiping Li, Chris Albanese, Mahadev Rao, Dolores Di Vizio, Salimuddin Shah, Stephen W. Byers, Radma Mahmood, Leonard H. Augenlicht, Robert Russell, Richard G. Pestell

Research output: Contribution to journalArticle

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Abstract

Constitutive β-catenin/Tcf activity, the primary transforming events in colorectal carcinoma, occurs through induction of the Wnt pathway or APC gene mutations that cause familial adenomatous polyposis. Mice carrying Ape mutations in their germ line (ApcMin) develop intestinal adenomas. Here, the crossing of ApcMin with cyclin D1-/- mice reduced the intestinal tumor number in animals genetically heterozygous or nullizygous for cyclin D1. Decreased tumor number in the duodenum, intestines, and colons of ApcMin/cyclin D1+/- mice correlated with reduced cellular proliferation and increased differentiation. Cyclin D1 deficiency reduced DNA synthesis and induced differentiation of colonic epithelial cells harboring mutant APC but not wild-type APC cells in vivo. In previous studies, the complete loss of cyclin D1 through homozygous genetic deletion conveyed breast tumor resistance. The protection of mice, genetically predisposed to intestinal tumorigenesis, through cyclin D1 heterozygosity suggests that modalities that reduce cyclin D1 abundance could provide chemoprotection.

Original languageEnglish (US)
Pages (from-to)7598-7611
Number of pages14
JournalMolecular and Cellular Biology
Volume24
Issue number17
DOIs
StatePublished - Sep 2004
Externally publishedYes

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Cyclin D1
Cell Differentiation
Epithelial Cells
Neoplasms
APC Genes
Catenins
Mutation
Wnt Signaling Pathway
Adenomatous Polyposis Coli
Hominidae
Duodenum
Germ Cells
Adenoma
Intestines
Colorectal Neoplasms
Colon
Carcinogenesis
Cell Proliferation
Breast Neoplasms
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice. / Hulit, James; Wang, Chenguang; Li, Zhiping; Albanese, Chris; Rao, Mahadev; Di Vizio, Dolores; Shah, Salimuddin; Byers, Stephen W.; Mahmood, Radma; Augenlicht, Leonard H.; Russell, Robert; Pestell, Richard G.

In: Molecular and Cellular Biology, Vol. 24, No. 17, 09.2004, p. 7598-7611.

Research output: Contribution to journalArticle

Hulit, J, Wang, C, Li, Z, Albanese, C, Rao, M, Di Vizio, D, Shah, S, Byers, SW, Mahmood, R, Augenlicht, LH, Russell, R & Pestell, RG 2004, 'Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice', Molecular and Cellular Biology, vol. 24, no. 17, pp. 7598-7611. https://doi.org/10.1128/MCB.24.17.7598-7611.2004
Hulit, James ; Wang, Chenguang ; Li, Zhiping ; Albanese, Chris ; Rao, Mahadev ; Di Vizio, Dolores ; Shah, Salimuddin ; Byers, Stephen W. ; Mahmood, Radma ; Augenlicht, Leonard H. ; Russell, Robert ; Pestell, Richard G. / Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 17. pp. 7598-7611.
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