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A mouse model of rhabdomyosarcoma originating from the adipocyte lineage.

ABSTRACT: Rhabdomyosarcoma (RMS) is an aggressive skeletal muscle-lineage tumor composed of malignant myoblasts that fail to exit the cell cycle and are blocked from fusing into syncytial muscle. Rhabdomyosarcoma includes two histolopathologic subtypes: alveolar rhabdomyosarcoma, driven by the fusion protein PAX3-FOXO1 or PAX7-FOXO1, and embryonal rhabdomyosarcoma (ERMS), which is genetically heterogeneous. Here, we show that adipocyte-restricted activation of Sonic hedgehog signaling through expression of a constitutively active Smoothened allele in mice gives rise to aggressive skeletal muscle tumors that display the histologic and molecular characteristics of human ERMS with high penetrance. Our findings suggest that adipocyte progenitors can be a cell of origin for Sonic hedgehog-driven ERMS, showing that RMS can originate from nonskeletal muscle precursors.

SUBMITTER: Hatley ME

PROVIDER: S-EPMC3479681 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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A mouse model of rhabdomyosarcoma originating from the adipocyte lineage.

Hatley Mark E ME Tang Wei W Garcia Matthew R MR Finkelstein David D Millay Douglas P DP Liu Ning N Graff Jonathan J Galindo Rene L RL Olson Eric N EN

Cancer cell 20121001 4

Rhabdomyosarcoma (RMS) is an aggressive skeletal muscle-lineage tumor composed of malignant myoblasts that fail to exit the cell cycle and are blocked from fusing into syncytial muscle. Rhabdomyosarcoma includes two histolopathologic subtypes: alveolar rhabdomyosarcoma, driven by the fusion protein PAX3-FOXO1 or PAX7-FOXO1, and embryonal rhabdomyosarcoma (ERMS), which is genetically heterogeneous. Here, we show that adipocyte-restricted activation of Sonic hedgehog signaling through expression o ...[more]

PMID: 23079662

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A mouse model of rhabdomyosarcoma originating from the adipocyte lineage

Project description:Activation of Sonic Hedgehog signaling through expression of a constitutively active Smoothened allele under control of an aP2 adipocyte-restricted transgene in mice gives rise to aggressive skeletal muscle tumors that display the histologic and molecular characteristics of human embryonal rhabdomyosarcoma with high penetrance. Conditional mouse models of embryonal rhabdomyosarcoma were created by activation of the oncogenic SmoM2 allele by both the non-muscle aP2-Cre or myotube Myogenin-Cre.

2012-10-22 | E-GEOD-40359 | biostudies-arrayexpress

A mouse model of rhabdomyosarcoma originating from the adipocyte lineage

2012-10-22 | GSE40359 | GEO

Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma.

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A novel mouse model of rhabdomyosarcoma underscores the dichotomy of MDM2-ALT1 function in vivo.

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