Expression of protooncogenes in murine osteosarcomas

Schön, Annemarie; Michiels, Luc; Janowski, M; Merregaert, J.; Erfle, Volker

doi:10.1002/ijc.2910380112

Cited by 28 publications

(13 citation statements)

References 49 publications

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“…On the other hand, c-myc levels in U-2 OS cells are known to be relatively high. In many osteosarcomas, the c-myc gene is amplified (17,37). Therefore, we were able to detect FIG.…”

Section: Resultsmentioning

confidence: 99%

Interference with the Expression of a Novel Human Polycomb Protein, hPc2, Results in Cellular Transformation and Apoptosis

Satijn

Olson

Vlag

et al. 1997

Molecular and Cellular Biology

108

123

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Polycomb (Pc) is involved in the stable and heritable repression of homeotic gene activity during Drosophila development. Here, we report the identification of a novel human Pc homolog, hPc2. This gene is more closely related to a Xenopus Pc homolog, XPc, than to a previously described human Pc homolog, CBX2 (hPc1). However, the hPc2 and CBX2/hPc1 proteins colocalize in interphase nuclei of human U-2 OS osteosarcoma cells, suggesting that the proteins are part of a common protein complex. To study the functions of the novel human Pc homolog, we generated a mutant protein, ⌬hPc2, which lacks an evolutionarily conserved C-terminal domain. This C-terminal domain is important for hPc2 function, since the ⌬hPc2 mutant protein which lacks the C-terminal domain is unable to repress gene activity. Expression of the ⌬hPc2 protein, but not of the wild-type hPc2 protein, results in cellular transformation of mammalian cell lines as judged by phenotypic changes, altered marker gene expression, and anchorage-independent growth. Specifically in ⌬hPc2-transformed cells, the expression of the c-myc proto-oncogene is strongly enhanced and serum deprivation results in apoptosis. In contrast, overexpression of the wild-type hPc2 protein results in decreased c-myc expression. Our data suggest that hPc2 is a repressor of proto-oncogene activity and that interference with hPc2 function can lead to derepression of proto-oncogene transcription and subsequently to cellular transformation.

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“…On the other hand, c-myc levels in U-2 OS cells are known to be relatively high. In many osteosarcomas, the c-myc gene is amplified (17,37). Therefore, we were able to detect FIG.…”

Section: Resultsmentioning

confidence: 99%

Interference with the Expression of a Novel Human Polycomb Protein, hPc2, Results in Cellular Transformation and Apoptosis

Satijn

Olson

Vlag

et al. 1997

Molecular and Cellular Biology

108

123

View full text Add to dashboard Cite

show abstract

“…In screening a number of spontaneous and radiation-induced murine osteosarcomas, a variety of oncogenes were found to be expressed, including c- abl , c- bas , c- fos , K- ras , and c- myc . No particular oncogene appeared to predominate [44]. So important were these oncogenes felt to be initially that a theory became prominent in the literature during the 1980s and 1990s that radiation-induced osteosarcomagenesis may have as much to do with unsilencing of oncogenes as it does with DNA and chromosomal damage [45, 46].…”

Section: Oncogenesmentioning

confidence: 99%

Osteosarcomagenesis: Modeling Cancer Initiation in the Mouse

Jones

2011

Sarcoma

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Osteosarcoma remains a deadly malignancy afflicting adolescents and young adults. The lack of a precursor and the panoply of genetic aberrations present in identified osteosarcomas makes study of its initiation difficult. A number of candidate hypotheses have been tested in the mouse, a species with a higher background incidence of osteosarcoma. Chemical carcinogens, external beam radiation, and bone-seeking heavy metal radioisotopes have all proven to be osteosarcomagenic in wild-type mice. A number of oncogenes, introduced via integrating viruses or aberrantly activated from heritable genetic loci, participate in and can individually drive osteosarcomagenesis. Germline and conditional gene ablations in the form of some but not all aneuploidy-inducing genes, conventional tumor suppressors, and factors that function normally in mesenchymal differentiation have also proven osteosarcomagenic, especially in combinations that silence the Rb1 and p53 pathways. This paper reviews the rich history of mouse models of osteosarcomagenesis, what they have taught us about the human disease, and what future mouse experiments yet promise to teach.

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“…Several proto-oncogenes are known to be expressed in osteosarcomas [3,17,19,26,30], but their roles in the pathogenesis of these tumors are incompletely understood. Likewise, the roles of proto-oncogenes in the development of other musculoskeletal lesions remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Detection of c‐fos expression in benign and malignant musculoskeletal lesions

Weisstein

Majeska

Klein

et al. 2001

Journal Orthopaedic Research

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The proto-oncogene c-fos has been implicated in the development of both benign and malignant lesions of bone. Although c-fos expression in such lesions has been well studied in transgenic mouse models, less is known about its role in human musculoskeletal pathology. To clarify this relationship, we used in situ hybridization to localize c-fos m-RNA transcripts in 26 fibrous lesions (eight cases of extra-abdominal fibromatosis and six cases each of fibrous dysplasia, fibrosarcoma, and malignant fibrous histiocytoma of bone) as well as six chondrosarcomas and eight conventional high grade osteosarcomas. We found detectable levels of c-fos expression in tissues from each type of lesion tested. Moreover, all fibrous lesions consistently demonstrated high levels of expression in a majority of cells in each lesion. Chondrosarcomas and osteosarcomas exhibited more heterogeneity in c-fos expression than fibrous tissues. Three of six chondrosarcomas showed moderate expression of c-fos while only one of six was considered high. Similarly, only three of eight osteosarcomas had high expression of c-fos. These findings indicate that the expression of c-fos may be important in the development of a broad range of fibrous lesions as well as in bone and cartilaginous tumors. Additionally, this is the first report, to our knowledge, of detectable c-fos m-RNA in human chondrosarcoma.

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Expression of protooncogenes in murine osteosarcomas

Cited by 28 publications

References 49 publications

Interference with the Expression of a Novel Human Polycomb Protein, hPc2, Results in Cellular Transformation and Apoptosis

Interference with the Expression of a Novel Human Polycomb Protein, hPc2, Results in Cellular Transformation and Apoptosis

Osteosarcomagenesis: Modeling Cancer Initiation in the Mouse

Detection of c‐fos expression in benign and malignant musculoskeletal lesions

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