Gadd45 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 extremelylethal form of human cancer, but the biological characteristicsrelated to their aggressive nature are not understood. Moreover,Gadd45 family proteins have been implicated in a variety ofgrowth-regulatory mechanisms, including DNA replication andrepair, G2/M checkpoint control, and apoptosis. In this studywe found that Gadd45 RNA was present at significantly lowerlevels in anaplastic cancer cells, compared with normal primarycultured thyrocytes. In addition, the adenovirus-mediated reexpressionof Gadd45 significantly inhibited the proliferation of anaplasticthyroid carcinoma cells, ARO, FRO, and NPA cells, which wasattributed to apoptosis. Furthermore, the adenovirus-mediateddelivery of Gadd45 gene in anaplastic thyroid cancer resultedin the inhibition of tumor growth in vivo. This in vitro andin vivo activity of the adenovirus-mediated transduction ofCR6/Gadd45, on anaplastic thyroid cancer cell growth suppression,was reminiscent of the effects of p53. This study demonstratesthat the Gadd45 gene has potential use as a candidate gene forgene 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-terminalkinase; MOI, multiplicity of infection; MTT, dimethylthiazoldiphenyltetra-zoliumbromide;SDS, sodium dodecyl sulfate; SSC, saline sodium citrate; TUNEL,terminal deoxynucleotidyltransferase-mediated deoxyuridine 5-triphosphatenick end labeling.
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