Enhanced SMYD3 expression is essential for the growth of breast cancer cells.
We previously reported that upregulation of SMYD3, a histone H3 lysine-4-specific methyltransferase, plays a key role in the proliferation of colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC). In the present study, we reveal that SMYD3 expression is also elevated in the great majority of breast cancer tissues. Similarly to CRC and HCC, silencing of SMYD3 by small interfering RNA to this gene resulted in the inhibited growth of breast cancer cells, suggesting that increased SMYD3 expression is also essential for the proliferation of breast cancer cells. Moreover, we show here that SMYD3 could promote breast carcinogenesis by directly regulating expression of the proto-oncogene WNT10B. These data imply that augmented SMYD3 expression plays a crucial role in breast carcinogenesis, and that inhibition of SMYD3 should be a novel therapeutic strategy for treatment of breast cancer.
Hamamoto
Ryuji
R
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Silva
Fabio Pittella
FP
Tsuge
Masataka
M
Nishidate
Toshihiko
T
Katagiri
Toyomasa
T
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C491119:WNT10B protein, human; D051153:Wnt Proteins; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human