Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis.
Oncogene
; 27(9): 1231-42, 2008 Feb 21.
Article
in En
| MEDLINE
| ID: mdl-17724472
ABSTRACT
Cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and polyubiquitination by SCF(FBX4-alphaB 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mammary Neoplasms, Animal
/
Cyclin D1
/
Active Transport, Cell Nucleus
/
Mammary Neoplasms, Experimental
Type of study:
Etiology_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2008
Document type:
Article
Affiliation country:
United States