Effects of SMYD3 Over-expression on Cell Cycle Acceleration and Cell Proliferation in MDA-MB-231 Human Breast Cancer Cells

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2010 Oct 20

PMID 20957523

Citations 24

Authors

Tian-nian Ren

Jing-Song Wang

Yun-Mian He

Chang-Liang Xu

Shu-Zhen Wang

Tao Xi

Affiliations

Soon will be listed here.

Abstract

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.

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References

Luo X, Ding Y, Zhou Q, Ye L, Wang S, Xi T . SET and MYND domain-containing protein 3 decreases sensitivity to dexamethasone and stimulates cell adhesion and migration in NIH3T3 cells. J Biosci Bioeng. 2007; 103(5):444-50. DOI: 10.1263/jbb.103.444. View

Downward J . Ras signalling and apoptosis. Curr Opin Genet Dev. 1998; 8(1):49-54. DOI: 10.1016/s0959-437x(98)80061-0. View

Wade P . Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001; 23(12):1131-7. DOI: 10.1002/bies.10008. View

Kim J, To T, Ishida J, Morosawa T, Kawashima M, Matsui A . Alterations of lysine modifications on the histone H3 N-tail under drought stress conditions in Arabidopsis thaliana. Plant Cell Physiol. 2008; 49(10):1580-8. DOI: 10.1093/pcp/pcn133. View

Hamamoto R, Silva F, Tsuge M, Nishidate T, Katagiri T, Nakamura Y . Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci. 2006; 97(2):113-8. PMC: 11159510. DOI: 10.1111/j.1349-7006.2006.00146.x. View

Antonsson B . Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion. Cell Tissue Res. 2001; 306(3):347-61. DOI: 10.1007/s00441-001-0472-0. View

Cory S, Adams J . The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002; 2(9):647-56. DOI: 10.1038/nrc883. View

Miremadi A, Oestergaard M, Pharoah P, Caldas C . Cancer genetics of epigenetic genes. Hum Mol Genet. 2007; 16 Spec No 1:R28-49. DOI: 10.1093/hmg/ddm021. View

Hamon M, Batsche E, Regnault B, Tham T, Seveau S, Muchardt C . Histone modifications induced by a family of bacterial toxins. Proc Natl Acad Sci U S A. 2007; 104(33):13467-72. PMC: 1948930. DOI: 10.1073/pnas.0702729104. View

10.

Schmeck B, Beermann W, van Laak V, Zahlten J, Opitz B, Witzenrath M . Intracellular bacteria differentially regulated endothelial cytokine release by MAPK-dependent histone modification. J Immunol. 2005; 175(5):2843-50. DOI: 10.4049/jimmunol.175.5.2843. View

11.

Luo X, Zou J, Wang S, Zhang T, Xi T . Novobiocin decreases SMYD3 expression and inhibits the migration of MDA-MB-231 human breast cancer cells. IUBMB Life. 2009; 62(3):194-9. DOI: 10.1002/iub.288. View

12.

Zou J, Wang S, Yang J, Luo X, Xie J, Xi T . Knockdown of SMYD3 by RNA interference down-regulates c-Met expression and inhibits cells migration and invasion induced by HGF. Cancer Lett. 2009; 280(1):78-85. DOI: 10.1016/j.canlet.2009.02.015. View

13.

Obaya A, Sedivy J . Regulation of cyclin-Cdk activity in mammalian cells. Cell Mol Life Sci. 2002; 59(1):126-42. PMC: 11337483. DOI: 10.1007/s00018-002-8410-1. View

14.

Wang S, Luo X, Shen J, Zou J, Lu Y, Xi T . Knockdown of SMYD3 by RNA interference inhibits cervical carcinoma cell growth and invasion in vitro. BMB Rep. 2008; 41(4):294-9. DOI: 10.5483/bmbrep.2008.41.4.294. View

15.

Wang Y, Fischle W, Cheung W, Jacobs S, Khorasanizadeh S, Allis C . Beyond the double helix: writing and reading the histone code. Novartis Found Symp. 2004; 259:3-17. View

16.

Varambally S, Dhanasekaran S, Zhou M, Barrette T, Kumar-Sinha C, Sanda M . The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002; 419(6907):624-9. DOI: 10.1038/nature01075. View

17.

Suzuki M, Shigematsu H, Shames D, Sunaga N, Takahashi T, Shivapurkar N . Methylation and gene silencing of the Ras-related GTPase gene in lung and breast cancers. Ann Surg Oncol. 2006; 14(4):1397-404. DOI: 10.1245/s10434-006-9089-6. View

18.

Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva F, Li M . SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004; 6(8):731-40. DOI: 10.1038/ncb1151. View

19.

Zhao P, Zhong W, Ying X, Yuan Z, Fu J, Zhou Z . Manganese chloride-induced G0/G1 and S phase arrest in A549 cells. Toxicology. 2008; 250(1):39-46. DOI: 10.1016/j.tox.2008.05.016. View

20.

Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan J . Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell. 1995; 80(2):279-84. DOI: 10.1016/0092-8674(95)90410-7. View