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Knockdown of IG20 Gene Expression Renders Thyroid Cancer Cells Susceptible to Apoptosis

Department of Microbiology and Immunology (M.S., P.B., P.V.K., B.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Department of Internal Medicine, Endocrinology and Metabolism, and Biochemistry (T.P., F.P.), Section of Endocrinology and Metabolism, University of Siena, 53100 Siena, Italy; and Department of Pathology (Y.E.N.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Address all correspondence and requests for reprints to: Bellur S. Prabhakar, Ph.D., Department of Microbiology and Immunology, Room E 705 (MC 790), 835 South Wolcott Avenue, Chicago, Illinois 60612. E-mail: bprabhak{at}uic.edu.

Aim: The aim of the study was to investigate the expression and function of the IG20 gene in thyroid cancer cell survival, proliferation, and apoptosis.

Methods: We determined the expression levels of the major isoforms of IG20 by quantitative RT-PCR in normal and thyroid tumor tissues/cell lines. We evaluated the functional consequence of IG20 knockdown in WRO (follicular carcinoma) and FRO (anaplastic carcinoma) thyroid cancer cell lines by measuring spontaneous, TNF-related apoptosis-inducing ligand (TRAIL), and TNF-induced apoptosis.

Results: The IG20 gene expression levels were higher in benign and malignant thyroid tumors and in WRO and FRO cells relative to normal tissues. Predominantly, MADD and DENN-SV isoforms of IG20 gene were expressed. IG20 knockdown resulted in increased spontaneous, TRAIL-, and TNF-induced apoptosis in WRO, but not FRO, cells. FRO cell resistance to apoptosis is likely due to caspase-8 deficiency.

Conclusion: IG20 knockdown renders WRO cells more susceptible to spontaneous, TRAIL-, and TNF-induced apoptosis and thus demonstrates the prosurvival function of the IG20 gene in thyroid cancer. These observations, combined with overexpression of IG20 noted in thyroid tumor tissues, may suggest a potential role in thyroid cancer survival and growth and indicate that IG20 may be targeted either alone or in conjunction with TRAIL or TNF treatment in certain thyroid cancers.