&lt;i&gt;C-myc&lt;/i&gt; and &lt;i&gt;c-fos&lt;/i&gt; in Human Osteosarcoma: Prognostic Value of mRNA and Protein Expression

Gamberi, Gabriella; Benassi, Maria Serena; Böhling, Tom; Ragazzini, Paola; Molendini, Lara; Sollazzo, Maria Rosa; Pompetti, Franca; Merli, M.; Magagnoli, Giovanna; Balladelli, Alba; Picci, Piero

doi:10.1159/000011912

Cited by 171 publications

(140 citation statements)

References 28 publications

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“…For example, increased expression of the cyclin-dependent kinase, cyclin DI, has been implicated as a mechanism through which c-fos may induce bone tumor formation [32]. On the other hand, recent studies have shown that overexpression of c-fos either alone [26] or in conjunction with other oncogenes [12] is often a characteristic of osteosarcomas with metastatic potential. In these instances, high c-fos expression would appear to be related more closely to proliferation than to active matrix production.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Although deregulation of c-MYC in human OS has been reported, the potential role of c-MYC in the pathogenesis of human OS is still unclear (Barrios et al, 1994;Gamberi et al, 1998). To analyze the significance Adipogenic potential regulates tumorigenic activity in OS T Shimizu et al of c-MYC expression in human OS, we examined 23 OS specimens by gene expression profiling.…”

Section: Ink4a-myc Bmscs Form Os In Syngeneic Micementioning

confidence: 99%

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

et al. 2010

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The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (À/À) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARc in tripotent MSC-like cells and overexpressing PPARc in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS.

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“…In osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and adverse outcome (Gamberi et al, 1998;Bamberger et al, 2001). In a comparative analysis between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions (Prusty and Das, 2005).…”

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confidence: 95%

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

et al. 2008

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Members of the Fos protein family dimerise with Jun proteins to form the AP-1 transcription factor complex. They have a central function in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumour progression. We analysed the expression of c-Fos, FosB, Fra-1 and Fra-2 to investigate the function of Fos transcription factors in ovarian cancer. A total of 101 patients were included in the study. Expression of Fos proteins was determined by western blot analysis, quantified by densitometry and verified by immunohistochemistry. Reduced c-Fos expression was independently associated with unfavourable progression-free survival (20.6, 31.6 and 51.2 months for patients with low, moderate and high c-Fos expression; P ¼ 0.003) as well as overall survival (23.8, 46.0 and 55.5 months for low, moderate and high c-Fos levels; P ¼ 0.003). No correlations were observed for FosB, Fra-1 and Fra-2. We conclude that loss of c-Fos expression is associated with tumour progression in ovarian carcinoma and that c-Fos may be a prognostic factor. These results are in contrast to the classic concept of c-Fos as an oncogene, but are supported by the recently discovered tumour-suppressing and proapoptotic function of c-Fos in various cancer types.

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<i>C-myc</i> and <i>c-fos</i> in Human Osteosarcoma: Prognostic Value of mRNA and Protein Expression

Cited by 171 publications

References 28 publications

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

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

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

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