The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.

Authors:
Ratna Kumari
Ratna Kumari
Lawrence J. Ellison Musculoskeletal Research Center
Sacramento | United States
Huan Li
Huan Li
Key Laboratory of Environmental and Applied Microbiology
China
Prof. Dominik R Haudenschild, Ph.D.
Prof. Dominik R Haudenschild, Ph.D.
University of California Davis Medical Center
Professor
Arthritis Research
Sacramento, CA | United States
Fernando Fierro
Fernando Fierro
Institute for Regenerative Cures
Sacramento | United States
Cathy S Carlson
Cathy S Carlson
College of Veterinary Medicine
College Station | United States
Lalita Gupta
Lalita Gupta
Molecular Parasitology and Vector Biology Laboratory
United States
Kavita Gupta
Kavita Gupta
University of Utah

Carcinogenesis 2012 Nov 30;33(11):2076-83. Epub 2012 Jul 30.

Department of Orthopaedic Surgery, Lawrence J. Ellison Musculoskeletal Research Center, University of California Davis Medical Center, Sacramento, CA 95817, USA.

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.

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November 2012
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