A murine model for the development of melanocytic nevi and their progression to melanoma.

Molecular Carcinogenesis
Tahseen H NastiCraig A Elmets

Abstract

Acquired melanocytic nevi are commonly found in sun exposed and unexposed human skin, but the potential for their transformation into invasive melanoma is not clear. Therefore, a mouse model of nevus initiation and progression was developed in C3H/HeN mice using a modified chemical carcinogenesis protocol. Nevi develop due to DNA damage initiated by dimethylbenz(a) anthracene (DMBA) followed by chronic promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Dysplastic pigmented skin lesions appeared in 7-9 wk with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 wk, but not in age matched controls. Immunohistochemistry, real-time PCR, and flow cytometric analyses confirmed their melanocytic origin. Transformed cells were present in a subset of nevi and dLNs, which exhibited anchorage-independent growth, tumor development, and metastasis in nude mice. Approximately 50% of the cell lines contained H-Ras mutations and lost tumor suppressor p16(Ink4a) expression. While most studies of melanoma focus on tumor progression in transgenic mouse models where the mutations are present from birth, our model permits investigation of acquired mutations at the earliest stages of nev...Continue Reading

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Citations

Aug 25, 2015·Pigment Cell & Melanoma Research·Mi Ryung RohHensin Tsao
Dec 23, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tahseen H NastiCraig A Elmets
Nov 15, 2017·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Prue H Hart, Mary Norval
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Mar 12, 2019·The Australasian Journal of Dermatology·Nima Mesbah Ardakani
Jan 30, 2019·Nature Cell Biology·Jianping GuoWenyi Wei
Nov 6, 2020·Cancer Prevention Research·Tahseen H NastiCraig A Elmets

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Methods Mentioned

BETA
PCR
transgenic
biopsies
biopsy
RNAseq

Software Mentioned

FACSDiva
Bowtie
BD
FlowJo
TopHat
Integrative Genomics Viewer ( IGV
ImagePro Plus
Integrative Genomics Viewer

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