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

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.

• Authors: Ratna Kumari, Huan Li, Dominik R Haudenschild, Fernando Fierro, Cathy S Carlson, Paula Overn, Lalita Gupta, Kavita Gupta, Jan Nolta, Jasper H N Yik, Paul E Di Cesare
• Journal: Carcinogenesis (Carcinogenesis) Vol. 33 Issue 11 Pg. 2076-83 (Nov 2012) ISSN: 1460-2180 [Electronic] England
• PMID: 22847180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• DNA-Binding Proteins
• RNA, Small Interfering
• TP53 protein, human
• Transcription Factors
• Tumor Suppressor Protein p53
• ZBTB7A protein, human
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Bone Neoplasms (drug therapy, metabolism, pathology)
• Cell Adhesion (drug effects)
• Cell Cycle (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chondrosarcoma (drug therapy, metabolism, pathology)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Humans
• Immunoenzyme Techniques
• Neoplasm Grading
• Oncogenes
• Prognosis
• RNA, Small Interfering (genetics)
• Tissue Array Analysis
• Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)