The Presence of Trail–opg Complex in Human Osteosarcoma and Human Salivary Gland Adenocarcinoma

Mogi, Makio; Kondo, Ayami

doi:10.1080/15321819.2010.538110

Cited by 1 publication

(1 citation statement)

References 22 publications

(33 reference statements)

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“…Another gene of interest, linked to the same genomic region as c-Myc, is osteoprotegerin (OPG). OPG is secreted by osteoblasts and acts as a decoy receptor to inhibit bone resorption and is produced by human OS lines [49,50]. These analyses suggest that pre-osteoblasts/ osteoblasts undergo a recurrent path that involves inactivation of both the p53 and Rb pathways, a gain of Myc (Chr 15 gain/rearrangement) and the reduction in gene dosage of chromosome 7.…”

Section: Discussionmentioning

confidence: 96%

Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA

Mutsaers

Baker

et al. 2013

Bone

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Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents. Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes. We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre:lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans. We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype. In contrast to other osteosarcoma models that have used Cre:lox mediated gene deletion, this model was generated through shRNA-based knockdown of p53. As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre:lox and shRNA. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer.

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Section: Discussionmentioning

confidence: 96%