Related Experiment Video

Updated: Sep 14, 2026

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 27, 2014

Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E

Damon B Bowe1, Nicholas J Kenney, Yair Adereth

  • 1Laboratory of Cancer Genomics, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, SC 29425, USA.

Oncogene
|January 23, 2002
PubMed

Insights

Cyclin D1 is crucial for HER2/Neu-driven breast cancer development. Its absence halts tumor formation, but cyclin E can compensate, suggesting combined inhibition for treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • HER2/Neu receptor tyrosine kinase and cyclin D1 gene overexpression are common in human breast cancer.
  • Cyclin D1 plays a role in cell cycle regulation and cancer progression.

Purpose of the Study:

  • To investigate the functional importance of cyclin D1 in HER2/Neu-induced mammary oncogenesis.
  • To determine if cyclin D1 deficiency impacts tumor formation driven by wild-type or mutant HER2/Neu.

Main Methods:

  • Developed genetically engineered mouse models overexpressing wild-type or mutant HER2/Neu in a cyclin D1-deficient background.
  • Assessed mammary tumor formation and progression in these mouse models.

Main Results:

  • Absence of cyclin D1 significantly suppressed mammary tumor formation induced by both wild-type and mutant HER2/Neu.
  • Cyclin D1 is preferentially required for HER2/Neu-mediated signal transduction in mammary oncogenesis.
  • A subset of mutant HER2/Neu mice lacking cyclin D1 developed tumors due to compensatory upregulation of cyclin E.

Conclusions:

  • Cyclin D1 is essential for HER2/Neu-driven mammary tumorigenesis.
  • Shared targets of cyclin D1 and cyclin E are critical for modulating HER2/Neu function.
  • Combined inhibition of cyclin D1 and cyclin E may offer a therapeutic strategy for HER2/Neu-induced malignancies.

More Related Videos

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

Related Concept Videos

Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...