Zang S, Ji Ch, Qu Xun, Dong X, Ma D, Ye J, Ma R, Dai J, Guo D
Department of Hematology, Qilu Hospital, Shandong University, Jinan, P. R. China.
Neoplasma. 2007;54(4):304-10.
Breast cancer is one of the leading causes of cancer death in women. The Notch family of proteins plays crucial roles in determining cell fates such as proliferation, differentiation and apoptosis. A role for Notch signaling in human breast cancer has been suggested by the development of adenocarcinomas in the murine mammary gland. However, it is not clear currently whether Notch signaling is frequently expressed and activated in breast cancers. Here we show that Notch signaling is overexpressed and highly activated in breast cancers. More significantly, the attenuation of Notch signaling by gamma-secretase inhibitor can inhibit the proliferation of breast cancer cells by both causing cell cycle arrest and apoptosis. Thus, targeting Notch signaling may be of therapeutic value in breast cancers.
乳腺癌是女性癌症死亡的主要原因之一。Notch蛋白家族在决定细胞命运(如增殖、分化和凋亡)方面发挥着关键作用。小鼠乳腺腺癌的发展提示了Notch信号在人类乳腺癌中的作用。然而,目前尚不清楚Notch信号在乳腺癌中是否经常表达和激活。在此我们表明,Notch信号在乳腺癌中过表达且高度激活。更重要的是,γ-分泌酶抑制剂对Notch信号的减弱可通过导致细胞周期停滞和凋亡来抑制乳腺癌细胞的增殖。因此,靶向Notch信号可能对乳腺癌具有治疗价值。