Hamamoto Ryuji, Silva Fabio Pittella, Tsuge Masataka, Nishidate Toshihiko, Katagiri Toyomasa, Nakamura Yusuke, Furukawa Yoichi
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.
Cancer Sci. 2006 Feb;97(2):113-8. doi: 10.1111/j.1349-7006.2006.00146.x.
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.
我们之前报道过,组蛋白H3赖氨酸-4特异性甲基转移酶SMYD3的上调在结直肠癌(CRC)和肝细胞癌(HCC)的增殖中起关键作用。在本研究中,我们发现绝大多数乳腺癌组织中SMYD3的表达也升高。与CRC和HCC相似,通过小干扰RNA沉默该基因的SMYD3导致乳腺癌细胞生长受到抑制,这表明SMYD3表达增加对乳腺癌细胞的增殖也至关重要。此外,我们在此表明SMYD3可通过直接调节原癌基因WNT10B的表达来促进乳腺癌发生。这些数据表明,SMYD3表达增加在乳腺癌发生中起关键作用,抑制SMYD3应是治疗乳腺癌的一种新的治疗策略。