A Mouse Model of Rhabdomyosarcoma Originating from the Adipocyte Lineage

被引：107

作者：

Hatley, Mark E. ^{[1
,2
,5
]}

Tang, Wei ^{[3
]}

Garcia, Matthew R. ^{[1
,2
,5
]}

Finkelstein, David ^{[6
]}

Millay, Douglas P. ^{[1
]}

Liu, Ning ^{[1
]}

Graff, Jonathan ^{[3
]}

Galindo, Rene L. ^{[1
,2
,4
]}

Olson, Eric N. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[5] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[6] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA

来源：

CANCER CELL | 2012年 / 22卷 / 04期

基金：

美国国家卫生研究院;

关键词：

BROWN ADIPOSE-TISSUE; EMBRYONAL RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; GENE-EXPRESSION; TRANSGENIC MICE; SATELLITE CELLS; SONIC HEDGEHOG; FAMILY-MEMBERS; FAT; CRE;

D O I：

10.1016/j.ccr.2012.09.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：536 / 546

页数：11

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