Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis

D. I. Lin, M. D. Lessie, A. B. Gladden, C. H. Bassing, Kay-Uwe Wagner, J. A. Diehl

Research output: Contribution to journalArticle

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Abstract

Cyclin D1 levels are maintained at steady state by phosphorylation- dependent nuclear export and polyubiquitination by SCF FBX4-αB crystallin . Inhibition of cyclin D1 proteolysis has been implicated as a causative factor leading to its overexpression in breast and esophageal carcinomas; however, the contribution of stable cyclin D1 to the genesis of such carcinomas has not been evaluated. We therefore generated transgenic mice wherein expression of either wild-type or a stable cyclin D1 allele (D1T286A) is regulated by MMTV-LTR. MMTV-D1T286A mice developed mammary adenocarcinomas at an increased rate relative to MMTV-D1 mice. Similar to human cancers that overexpress cyclin D1, D1T286A tumors were estrogen receptor-positive and exhibited estrogen-dependent growth. Collectively, these results suggest that temporal control of cyclin D1 subcellular localization and proteolysis is critical for maintenance of homeostasis within the mammary epithelium.

Original languageEnglish (US)
Pages (from-to)1231-1242
Number of pages12
JournalOncogene
Volume27
Issue number9
DOIs
StatePublished - Feb 21 2008

Fingerprint

Cell Nucleus Active Transport
Cyclin D1
Proteolysis
Carcinogenesis
Breast
Crystallins
Estrogen Receptors
Transgenic Mice
Neoplasms
Estrogens
Adenocarcinoma
Homeostasis
Epithelium
Alleles
Maintenance
Phosphorylation
Breast Neoplasms
Carcinoma
Growth

Keywords

  • CDK4
  • Cyclin D1
  • FBX4
  • Mammary gland
  • PD0332991

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lin, D. I., Lessie, M. D., Gladden, A. B., Bassing, C. H., Wagner, K-U., & Diehl, J. A. (2008). Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene, 27(9), 1231-1242. https://doi.org/10.1038/sj.onc.1210738

Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. / Lin, D. I.; Lessie, M. D.; Gladden, A. B.; Bassing, C. H.; Wagner, Kay-Uwe; Diehl, J. A.

In: Oncogene, Vol. 27, No. 9, 21.02.2008, p. 1231-1242.

Research output: Contribution to journalArticle

Lin, DI, Lessie, MD, Gladden, AB, Bassing, CH, Wagner, K-U & Diehl, JA 2008, 'Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis', Oncogene, vol. 27, no. 9, pp. 1231-1242. https://doi.org/10.1038/sj.onc.1210738
Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner K-U, Diehl JA. Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene. 2008 Feb 21;27(9):1231-1242. https://doi.org/10.1038/sj.onc.1210738
Lin, D. I. ; Lessie, M. D. ; Gladden, A. B. ; Bassing, C. H. ; Wagner, Kay-Uwe ; Diehl, J. A. / Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. In: Oncogene. 2008 ; Vol. 27, No. 9. pp. 1231-1242.
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