Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells.
SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase that plays an important role in transcriptional regulation in human carcinogenesis. It can specifically methylate histone H3 at lysine 4 and activate the transcription of a set of downstream genes, including several oncogenes (e.g., N-myc, CrkL, Wnt10b, RIZ and hTERT) and genes involved in the control of cell cycle (e.g., CyclinG1 and CDK2) and signal transduction (e.g., STAT1, MAP3K11 and PIK3CB). To determine the effects of SMYD3 over-expression on cell proliferation, we transfected SMYD3 into MDA-MB-231 cells and found that these cells showed several transformed phenotypes as demonstrated by colony growth in soft agar. Besides, we show here that down-regulation of SMYD3 could induce G1-phase cell cycle arrest, indicating the potent induction of apoptosis by SMYD3 knockdown. These results suggest the regulatory mechanisms of SMYD3 on the acceleration of cell cycle and facilitate the development of strategies that may inhibit the progression of cell cycle in breast cancer cells.
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China. rentiannian@163.com
Tian-nian
TN
Ren
Jing-song
JS
Wang
Yun-mian
YM
He
Chang-liang
CL
Xu
Shu-zhen
SZ
Wang
Tao
T
Xi
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans
D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human