Abstract A24: The transcriptional regulator JAB1 is a novel regulator of osteosarcoma development

Osteosarcoma is the most common malignant primary bone tumor. Osteosarcoma patients with metastases have a survival rate of only 25%. Therefore, a greater understanding of the pathogenesis of osteosarcoma is needed for better diagnosis and treatment. An emerging player in tumorigenesis is the transcriptional cofactor JAB (also named CSN5, COPS5), through its effects on cell proliferation, differentiation, survival, and cell cycle progression. Our laboratory has recently shown that Jab1 plays critical roles in the successive steps of mouse skeletal development by affecting master developmental regulators Runx2 and Sox9 in a context-dependent manner. As an essential component of the highly conserved COP9 signalosome complex, JAB1 is over-expressed in many different types of cancers, including breast and lung, but has not been studied in bone cancer. Thus, the goal of this study is to determine the potential role of JAB1 in the pathogenesis of osteosarcoma. We first determined, by immunohistochemistry, that JAB1 was highly expressed in over 75% of fifty-one osteosarcoma patients’ biopsy samples. Next, to determine whether down-regulating JAB1 expression in osteosarcoma reduces tumorigenesis, we knocked down JAB1 expression in a highly metastatic osteosarcoma cell line 143B, using shRNA lentiviral vectors. The JAB1 knockdown cells exhibited significantly reduced cell proliferation, colony formation, and motility compared with the control cells. Therefore, these results sugg...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Pediatric Cancers and Development: Poster Presentations - Proffered Abstracts Source Type: research