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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 8 3913-3920
Copyright © 2003 by The Endocrine Society

Gadd45{gamma} Expression Is Reduced in Anaplastic Thyroid Cancer and Its Reexpression Results in Apoptosis

Hyo Kyun Chung, Yong-Weon Yi, Neon-Cheol Jung, Daegun Kim, Jae Mi Suh, Ho Kim, Ki Cheol Park, Dong Wook Kim, Eun Suk Hwang, Jeong Hun Song, Bon-Jeong Ku, Hee Jung Han, Heung Kyu Ro, Jin Man Kim and Minho Shong

Laboratory of Endocrine Cell Biology, National Research Laboratory Program, Departments of Internal Medicine (H.K.C., J.M.S., H.K., K.C.P., D.W.K., E.S.H., J.H.S., B.-J.K., H.J.H., H.K.R., M.S.) and Pathology (J.M.K.), Chungnam National University College of Medicine, Daejeon 301-721; Neurogenex Inc. (Y.-W.Y., N.-C.J.), Seoul 151-744; and Department of Biological Science (D.K.), Korea Advanced Institute of Science and Technology, Daejeon 301-721, Korea

Address all correspondence and requests for reprints to: Minho Shong, M.D., Laboratory of Endocrine Cell Biology, Department of Internal Medicine, Chungnam National University School of Medicine, 640 Daesadong Chungku, Taejon 301-040, Korea. E-mail: minhos{at}cnu.ac.kr.

Anaplastic thyroid carcinomas are a highly aggressive and extremely lethal form of human cancer, but the biological characteristics related to their aggressive nature are not understood. Moreover, Gadd45 family proteins have been implicated in a variety of growth-regulatory mechanisms, including DNA replication and repair, G2/M checkpoint control, and apoptosis. In this study we found that Gadd45{gamma} RNA was present at significantly lower levels in anaplastic cancer cells, compared with normal primary cultured thyrocytes. In addition, the adenovirus-mediated reexpression of Gadd45{gamma} significantly inhibited the proliferation of anaplastic thyroid carcinoma cells, ARO, FRO, and NPA cells, which was attributed to apoptosis. Furthermore, the adenovirus-mediated delivery of Gadd45{gamma} gene in anaplastic thyroid cancer resulted in the inhibition of tumor growth in vivo. This in vitro and in vivo activity of the adenovirus-mediated transduction of CR6/Gadd45{gamma}, on anaplastic thyroid cancer cell growth suppression, was reminiscent of the effects of p53. This study demonstrates that the Gadd45{gamma} gene has potential use as a candidate gene for gene therapy in anaplastic thyroid cancer.

This work was supported by National Research Laboratory Program (M1-0104-00-0014), Ministry of Science and Technology, Korea.

Abbreviations: CMV, Cytomegalovirus; FBS, fetal bovine serum; Gadd45, growth arrest- and DNA damage-induced gene; JNK, Jun-terminal kinase; MOI, multiplicity of infection; MTT, dimethylthiazoldiphenyltetra-zoliumbromide; SDS, sodium dodecyl sulfate; SSC, saline sodium citrate; TUNEL, terminal deoxynucleotidyltransferase-mediated deoxyuridine 5-triphosphate nick end labeling.




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