Related Experiment Video

Updated: May 26, 2026

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Combined effect of cyclin D3 expression and abrogation of cyclin D1 prevent mouse skin tumor development

Xian Wang1, Christopher Sistrunk, Paula L Miliani de Marval

  • 1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

Cell Cycle (Georgetown, Tex.)
|January 5, 2012
PubMed

Insights

Modulating D-type cyclins, specifically overexpressing cyclin D3 while reducing cyclin D1 and D2, significantly inhibits ras-mediated skin tumorigenesis in mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Ras-mediated skin tumorigenesis is linked to cyclin D1 and D2 signaling.
  • Cyclin D3 expression typically inhibits skin tumor development, contrasting with other D-type cyclins.
  • Understanding D-type cyclin family interactions is crucial for cancer research.

Purpose of the Study:

  • To investigate the combined effect of modulating D-type cyclin family members on skin tumorigenesis.
  • To develop and utilize a novel mouse model (K5D3/cyclin D1(-/-)) for studying these interactions.
  • To determine if simultaneous upregulation of cyclin D3 and downregulation of cyclin D1/D2 can inhibit tumor formation.

Main Methods:

  • Development of the K5D3/cyclin D1(-/-) compound mouse model.
  • Overexpression of cyclin D3 and ablation of cyclin D1 in mouse skin keratinocytes.
  • Analysis of cyclin D2 levels and keratinocyte proliferation.
  • Assessment of ras-mediated skin tumorigenesis in the developed mouse model.

Main Results:

  • The K5D3/cyclin D1(-/-) model showed reduced cyclin D2 levels, similar to K5D3 transgenic mice.
  • Induced cyclin D3 expression compensated for reduced cyclin D1 and D2, maintaining normal keratinocyte proliferation.
  • Simultaneous cyclin D1 ablation and cyclin D2 downregulation via cyclin D3 led to a significant reduction in ras-mediated skin tumorigenesis.

Conclusions:

  • Modulating specific D-type cyclin family members is a viable strategy to inhibit skin tumor development.
  • This approach shows particular promise for inhibiting ras-mediated tumorigenesis.
  • Targeting D-type cyclin interactions offers potential therapeutic avenues in oncology.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Related Concept Videos

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,...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...