Related Experiment Video
Updated: Jul 12, 2026

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis
D I Lin1, M D Lessie, A B Gladden
1Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
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.
More Related Videos
Related Concept Videos
Abnormal Proliferation
Inhibition of Cdk Activity
Positive Regulator Molecules
Positive Regulator Molecules
Anaphase Promoting Complex
Separation of Sister Chromatids
At the onset of anaphase, separase, a proteolytic enzyme, is...

