Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice

Nathalie Dhomen; Jorge S. Reis-Filho; Silvy da Rocha Dias; Robert Hayward; Kay Savage; Veronique Delmas; Lionel Larue; Catrin Pritchard; Richard Marais

doi:10.1016/j.ccr.2009.02.022

Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice

Nathalie Dhomen, Jorge S. Reis-Filho, Silvy da Rocha Dias, Robert Hayward, Kay Savage, Veronique Delmas, Lionel Larue, Catrin Pritchard, Richard Marais

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-review

Abstract

We show here that inducible expression of BrafV600E off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of BrafV600E mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16INK4a is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by BrafV600E expressed at physiological levels that reflects the genetics and pathology of the human disease. © 2009 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	294-303
Number of pages	9
Journal	Cancer Cell
Volume	15
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2009.02.022
Publication status	Published - 7 Apr 2009

Keywords

CELLCYCLE

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2009.02.022

Cite this

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title = "Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice",

abstract = "We show here that inducible expression of BrafV600E off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of BrafV600E mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16INK4a is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by BrafV600E expressed at physiological levels that reflects the genetics and pathology of the human disease. {\textcopyright} 2009 Elsevier Inc. All rights reserved.",

keywords = "CELLCYCLE",

author = "Nathalie Dhomen and Reis-Filho, {Jorge S.} and {da Rocha Dias}, Silvy and Robert Hayward and Kay Savage and Veronique Delmas and Lionel Larue and Catrin Pritchard and Richard Marais",

note = "C107/A10433, Cancer Research UK, United Kingdom",

year = "2009",

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journal = "Cancer Cell",

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TY - JOUR

T1 - Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice

AU - Dhomen, Nathalie

AU - Reis-Filho, Jorge S.

AU - da Rocha Dias, Silvy

AU - Hayward, Robert

AU - Savage, Kay

AU - Delmas, Veronique

AU - Larue, Lionel

AU - Pritchard, Catrin

AU - Marais, Richard

N1 - C107/A10433, Cancer Research UK, United Kingdom

PY - 2009/4/7

Y1 - 2009/4/7

N2 - We show here that inducible expression of BrafV600E off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of BrafV600E mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16INK4a is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by BrafV600E expressed at physiological levels that reflects the genetics and pathology of the human disease. © 2009 Elsevier Inc. All rights reserved.

AB - We show here that inducible expression of BrafV600E off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of BrafV600E mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16INK4a is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by BrafV600E expressed at physiological levels that reflects the genetics and pathology of the human disease. © 2009 Elsevier Inc. All rights reserved.

KW - CELLCYCLE

U2 - 10.1016/j.ccr.2009.02.022

DO - 10.1016/j.ccr.2009.02.022

M3 - Article

C2 - 19345328

SN - 1878-3686

VL - 15

SP - 294

EP - 303

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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