The role of TLE1 in synovial sarcoma.

Abstract

The treatment outcome of synovial sarcoma is poor owing to its resistance to radiation and chemotherapy. The transducin-like enhancer of split 1 (TLE1) is a co-repressor that involves many signaling pathways like cell survival, hematopoiesis and differentiation. Although TLE1 is uniquely expressed in synovial sarcomas, the biological role of TLE1 is not completely understood. This study evaluated the function of TLE1 in synovial sarcomas using knock-down of TLE1, and examined whether the inhibition of TLE1 suppresses the proliferation of synovial sarcomas and enhances the cytotoxicity caused by doxorubicin (doxo). The over-expression of TLE1 was first confirmed in synovial sarcoma cells (HS-SYII). When the HS-SYII cells and normal fibroblast were transiently transfected with TLE1 siRNA, the MTT assay revealed growth inhibition in the HS-SY-11 cells but not in the normal fibroblast. TLE1 silencing also potentiated the cytotoxic effects of doxo against HS-SYII cells. This effect of TLE1 silencing was attributed mainly to the induction of apoptosis. Subsequent analysis revealed that Bcl-2 is a possible downstream target of TLE1 signaling. This study demonstrated that TLE1 is a critical factor for the survival of synovial sarcomas. Overall, the inhibition of TLE1 affects cell proliferation and the apoptosis pathway by suppressing the expression of Bcl-2.

• Authors: Sung Wook Seo, Hyewon Lee, Hyun-Il Lee, Han-Soo Kim
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 29 Issue 7 Pg. 1131-6 (Jul 2011) ISSN: 1554-527X [Electronic] United States
• PMID: 21319215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Orthopaedic Research Society.

Chemical References

• Antibiotics, Antineoplastic
• Co-Repressor Proteins
• RNA, Small Interfering
• Repressor Proteins
• TLE1 protein, human
• Doxorubicin

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects, physiology)
• Cell Division (drug effects, physiology)
• Cell Line, Tumor
• Co-Repressor Proteins
• Doxorubicin (pharmacology)
• Fibroblasts (cytology, physiology)
• Gene Expression Regulation, Neoplastic
• Humans
• RNA, Small Interfering
• Repressor Proteins (genetics, physiology)
• Sarcoma, Synovial (drug therapy, pathology, physiopathology)
• Soft Tissue Neoplasms (drug therapy, pathology, physiopathology)