Related Experiment Video

Updated: Apr 26, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

13.3K

Targeted p16(Ink4a) epimutation causes tumorigenesis and reduces survival in mice

Da-Hai Yu, Robert A Waterland, Pumin Zhang

    The Journal of Clinical Investigation
    |July 26, 2014
    PubMed

    Insights

    Epigenetic changes, specifically DNA methylation, can drive cancer development. This study shows that altering methylation of the p16Ink4a gene in mice directly causes tumors, proving epimutations can initiate cancer.

    Area of Science:

    • Epigenetics
    • Cancer Biology
    • Molecular Oncology

    Background:

    • Cancer is often considered a genetic disease, but epigenetic alterations like DNA methylation are frequently observed.
    • The role of epimutations (aberrant epigenetic changes) in initiating tumorigenesis remains unclear.

    Purpose of the Study:

    • To investigate whether an epimutation can directly induce cancer.
    • To validate a targeted DNA methylation strategy for epigenetic engineering in vivo.

    Main Methods:

    • Engineered a system to induce targeted DNA methylation at the p16Ink4a promoter in mice.
    • Assessed the impact of induced hypermethylation on gene expression, tumor incidence, and survival.

    Main Results:

    • Targeted DNA methylation of the p16Ink4a promoter led to transcriptional suppression in aging mice.
    • Induced p16Ink4a hypermethylation increased spontaneous cancer incidence.
    • Mice with both germline p16Ink4a mutation and somatic epimutation showed accelerated tumor development.

    Conclusions:

    • Epimutations, specifically in the p16Ink4a gene, can directly drive tumor formation and progression.
    • Targeted DNA methylation is a validated approach for epigenetic engineering with implications for cancer research.

    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

    8.6K
    Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice10:13

    Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

    Published on: August 12, 2014

    13.1K

    Related Concept Videos

    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...
    4.0K
    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,...
    4.7K
    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...
    3.5K
    In-vitro Mutagenesis01:16

    In-vitro Mutagenesis

    To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
    14.8K
    Loss of Tumor Suppressor Gene Functions01:12

    Loss of Tumor Suppressor Gene Functions

    Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
    When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
    4.9K
    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...
    4.8K