Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells.
The SET and MYND domain-containing protein 3 (SMYD3) gene was found to encode a novel histone methyltransferase involved in human cancer cells. It could specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes, including of several oncogenes (e.g., N-Myc, CrkL, Wnt10b, RIZ, and hTERT) and genes involved in the control of cell cycle (e.g., Cyclin G1 and CDK2) and signal transduction (e.g., STAT1, MAP3K11, and PIK3CB). To determine the effects of SMYD3 overexpression on cell transformation, serum dependence and apoptosis sensitivity, we expressed SMYD3 in NIH3T3 cells, and these cells showed several transformed phenotypes as demonstrated by foci formation and colony growth in soft agar. Besides, these transfectants also showed increased serum dependence and depression of sensitivity to apoptosis induced by dexamethasone. These findings lend further understanding to the role of SMYD3 in the genesis of human cancers and might throw light on the development of novel therapeutic approaches to human cancers.
Luo
Xue-Gang
XG
Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
Xi
Tao
T
Guo
Shu
S
Liu
Zhi-Peng
ZP
Wang
Nan
N
Jiang
Yong
Y
Zhang
Tong-Cun
TC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D044967:Serum; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D003470:Culture Media; D012333:RNA, Messenger; D003907:Dexamethasone; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human