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The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.
- Source :
-
Carcinogenesis [Carcinogenesis] 2012 Nov; Vol. 33 (11), pp. 2076-83. Date of Electronic Publication: 2012 Jul 30. - Publication Year :
- 2012
-
Abstract
- Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.
- Subjects :
- Antibiotics, Antineoplastic pharmacology
Blotting, Western
Bone Neoplasms drug therapy
Bone Neoplasms metabolism
Cell Adhesion drug effects
Cell Cycle drug effects
Cell Movement drug effects
Cell Proliferation drug effects
Chondrosarcoma drug therapy
Chondrosarcoma metabolism
Cyclin-Dependent Kinase Inhibitor p21 metabolism
DNA-Binding Proteins antagonists & inhibitors
DNA-Binding Proteins genetics
Humans
Immunoenzyme Techniques
Neoplasm Grading
Prognosis
RNA, Small Interfering genetics
Tissue Array Analysis
Transcription Factors antagonists & inhibitors
Transcription Factors genetics
Tumor Cells, Cultured
Tumor Suppressor Protein p53 metabolism
Apoptosis drug effects
Bone Neoplasms pathology
Chondrosarcoma pathology
DNA-Binding Proteins metabolism
Doxorubicin pharmacology
Drug Resistance, Neoplasm
Oncogenes
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 33
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 22847180
- Full Text :
- https://doi.org/10.1093/carcin/bgs254