公开(公告)号：US20090075929A1

公开(公告)日：2009-03-19

申请号：US12174296

申请日：2008-07-16

申请人： Bellur S. Prabhakar ,  Nirupama Mulherkar

发明人： Bellur S. Prabhakar ,  Nirupama Mulherkar

IPC分类号： A61K31/7105 ,  C07H21/02 ,  G01N33/566 ,  A61P31/00 ,  C07K14/00 ,  C12N5/06

CPC分类号： C12N15/1135 ,  C12N15/113 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53

摘要： Methods and compositions inhibit the growth of cancer cells by selectively down-regulating the expression of an IG20 splice variant including MADD. Specific knock-down of MADD splice variant resulted in the apoptosis of cancer cells. Interfering RNAs including small hairpin RNAs (shRNA) to down-regulate MADD expression in vivo are disclosed. Inhibition of MADD phosphorylation by Akt results in activation of cancer cell death. Down-regulation of MADD expression results in switching to apoptotic mode due to lack of MAPK activation upon TNF-α-based induction.

摘要翻译： 方法和组合物通过选择性下调包括MADD的IG20剪接变体的表达来抑制癌细胞的生长。 MADD剪接变体的特异性敲低导致癌细胞凋亡。 公开了干扰RNA，包括小发夹RNA（shRNA）以体内MADD表达下调。 抑制Akt的MADD磷酸化导致癌细胞死亡的激活。 MADD表达的下调导致由于在基于TNF-α的诱导下缺乏MAPK激活而切换至凋亡模式。