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

Abstract

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.

A novel quinoline, MT477: suppresses cell signaling through Ras molecular pathway, inhibits PKC activity, and demonstrates in vivo anti-tumor activity against human carcinoma cell lines

“…5c), which is specifically activated through the ERK1/2 molecular pathway and is strongly implicated in regulating c-fos gene expression. Targeting c-fos expression may be a promising strategy for treating many different human cancers, such as sarcomas [34,35], breast cancer [36] and epitheloid adenocarcinoma [37]; therefore, indirect Elk1 inhibition by MT477 may represent a critical finding of our study.…”

Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice

“…Loss of p53, but not Rb alone, was sufficient to promote tumorigenesis, whereas the loss of both exhibited strong synergy. Other alterations in human OSA include high expression of MYC, MET, and FOS (23,24); transgenic FOS expression in mice results in bone sarcomas, some of which are osteogenic (25,26). Overall, the prevalence of widespread copy number alterations (CNAs) in OSA point to the existence of many unidentified OSA genes.…”

Animal Models in Osteosarcoma

“…Other genes such as C-FOS (77, 78) , TWIST (79) , p14ARF (80) , p16INK4a (81) , PRKAR1A (71), and p21CIP (82) have also been implicated in OS pathogenesis based on studies of human OS samples. Their mutation appears to complement the defects in the P53 and RB pathways, and their involvement in osteosarcomagenesis is also demonstrated from genetically engineered mouse models.…”