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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 daughter...
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...
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.
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Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
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Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

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Related Experiment Video

Updated: Jun 10, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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

Published on: June 7, 2019

Somatic p16(INK4a) loss accelerates melanomagenesis.

K B Monahan1, G I Rozenberg, J Krishnamurthy

  • 1Departments of Medicine and Genetics, The Lineberger Comprehensive Cancer Center, The Center for Environmental Health and Susceptibility, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7295, USA.

Oncogene
|August 11, 2010
PubMed
Summary

This study created a mouse model for melanoma by combining genetic events common in human cancers. The model demonstrates that activating K-Ras and losing p16INK4a and p53 rapidly induces invasive melanoma in adult mice.

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Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Human melanomas frequently exhibit loss of p16INK4a-RB and ARF-p53 tumor suppressor pathways, alongside RAS-RAF signaling activation.
  • While familial melanoma is linked to germline p16INK4a mutations, most cases arise from somatic events like p16INK4a loss and RAS mutations (N-RAS, B-RAF) or p53 inactivation.
  • Alternative genetic alterations, including K-RAS activation and p53 inactivation, also contribute to melanoma development.

Purpose of the Study:

  • To engineer a novel murine model of melanoma that recapitulates key somatic genetic events observed in human melanomas.
  • To investigate the synergistic effects of oncogenic K-Ras activation and the loss of p16INK4a and/or p53 tumor suppressor pathways in melanoma development.

Main Methods:

  • Developed a conditional p16INK4a-null allele.
  • Combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele, and a loxP-stop-loxP activatable oncogenic K-Ras allele.
  • Utilized this genetic engineering approach in mice to model melanoma formation.

Main Results:

  • Demonstrated potent synergy between melanocyte-specific K-Ras activation and the loss of p16INK4a and/or p53 in driving melanomagenesis.
  • Mice with these genetic alterations rapidly developed invasive, unpigmented, nonmetastatic melanomas with high penetrance.
  • Observed that these somatic genetic events can induce melanoma in adult mice, indicating sustained melanocyte susceptibility to transformation.

Conclusions:

  • The engineered murine model effectively mimics critical genetic events in human melanoma.
  • The combination of activated K-Ras and loss of p16INK4a/p53 is sufficient to rapidly induce invasive melanoma.
  • Melanocytes remain susceptible to transformation by these genetic events throughout adulthood, offering insights into melanoma pathogenesis.