Dataset Information


Modeling tumor subtypes in vivo using lineage restricted transgenic shRNA

ABSTRACT: Expression analysis from two genetically engineered mouse models of osteosarcoma determine the expression profile of mouse osteosarcoma Human osteosarcoma (OS) is comprised of three different subtypes: fibroblastic, chondroblastic and osteoblastic. We previously generated a mouse model of fibroblastic OS by conditional deletion of p53 and Rb in osteoblasts. Here we report an accurate mouse model of the osteoblastic subtype using shRNA-based suppression of p53. Like human OS, tumors frequently present in the long bones and preferentially disseminate to the lungs; features less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using different technology. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of a distinct clinical subtype of OS that was not previously represented and more fully recapitulated the clinical spectrum of this human tumor. Overall design: 4 primary tumors from Cre:lox OS model; 4 primary tumors from shRNA OS model.

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

ORGANISM(S): Mus musculus  

SUBMITTER: Carl Walkley  




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