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 language | English (US) |
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Pages (from-to) | 1231-1242 |
Number of pages | 12 |
Journal | Oncogene |
Volume | 27 |
Issue number | 9 |
DOIs | |
State | Published - Feb 21 2008 |
Keywords
- CDK4
- Cyclin D1
- FBX4
- Mammary gland
- PD0332991
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research