The proto‐oncogene function of Mdm2 in bone
| Autor: | Angela Bruzzaniti, Melissa A. Kacena, Ying Hua Cheng, Jung Min Hong, Christine M. Eischen, Robyn K. Fuchs, Lindsey D. Mayo, Daniel S. Perrien, R. Adam Hooker, David J. Olivos, Kristin T. Chun |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Osteoclasts Cell lineage Proto-Oncogene Mas Biochemistry Article Mice 03 medical and health sciences Calcification Physiologic 0302 clinical medicine Bone Density Osteogenesis Cell Line Tumor Proto-Oncogenes Animals Humans Copy-number variation neoplasms Molecular Biology Cellular Transformation Analysis of Variance Osteosarcoma Osteoblasts biology Oncogene Proto-Oncogene Proteins c-mdm2 Cell Biology Phenotype Mice Inbred C57BL 030104 developmental biology Mice Inbred DBA 030220 oncology & carcinogenesis Cancellous Bone biology.protein Cancer research Mdm2 Female Bone Remodeling Function (biology) Bone mass |
| Zdroj: | Journal of Cellular Biochemistry. 119:8830-8840 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.27133 |
| Popis: | Mouse double minute 2 (Mdm2) is a multifaceted oncoprotein that is highly regulated with distinct domains capable of cellular transformation. Loss of Mdm2 is embryonically lethal, making it difficult to study in a mouse model without additional genetic alterations. Global overexpression through increased Mdm2 gene copy number (Mdm2Tg) results in the development of hematopoietic neoplasms and sarcomas in adult animals. In these mice, we found an increase in osteoblastogenesis, differentiation, and a high bone mass (HBM) phenotype. Since it was difficult to discern the cell lineage that generated this phenotype, we generated osteoblast-specific Mdm2 overexpressing (Mdm2TgOb) mice in two different strains, C57BL/6 and DBA. These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization. Importantly, overexpression of Mdm2 corrected aged-related bone loss in mice, providing a role for the proto-oncogenic activity of Mdm2 in bone health of adult animals. |
| Databáze: | OpenAIRE |
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