Gadd45gamma expression is reduced in anaplastic thyroid cancer and its reexpression results in apoptosis.
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, G(2)/M checkpoint control, and apoptosis. In this study we found that Gadd45gamma RNA was present at significantly lower levels in anaplastic cancer cells, compared with normal primary cultured thyrocytes. In addition, the adenovirus-mediated reexpression of Gadd45gamma 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 Gadd45gamma 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/Gadd45gamma, on anaplastic thyroid cancer cell growth suppression, was reminiscent of the effects of p53. This study demonstrates that the Gadd45gamma gene has potential use as a candidate gene for gene therapy in anaplastic thyroid cancer.
Chung
Hyo Kyun
HK
Laboratory of Endocrine Cell Biology, National Research Laboratory Program, Chungnam National University College of Medicine, Daejeon 301-721, Korea.
Yi
Yong-Weon
YW
Jung
Neon-Cheol
NC
Kim
Daegun
D
Suh
Jae Mi
JM
Kim
Ho
H
Park
Ki Cheol
KC
Kim
Dong Wook
DW
Hwang
Eun Suk
ES
Song
Jeong Hun
JH
Ku
Bon-Jeong
BJ
Han
Hee Jung
HJ
Ro
Heung Kyu
HK
Kim
Jin Man
JM
Shong
Minho
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013778:Tetrazolium Salts; D013844:Thiazoles; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; D000097642:GADD45 Proteins; C022616:thiazolyl blue