c-FLIP gene silencing eliminates tumor cells in breast cancer xenografts without affecting stromal cells.
Cellular FLICE-like inhibitory protein (c-FLIP) is an inhibitor of death receptor-mediated apoptosis and exerts its anti-apoptotic function by blocking the activation of caspase-8. We recently showed that the siRNA-mediated knockdown of c-FLIP in MCF-7 breast cancer cells growing in vitro triggered apoptosis. The aim of this study was to determine if the in vivo knockdown of c-FLIP in MCF-7 breast cancer xenografts affected tumor viability. Immunohistochemical detection of c-FLIP in the tumor sections revealed that the knockdown of c-FLIP eliminated the neoplastic cells within the breast cancer xenografts without affecting the normal stromal and fibroblastic cells. These results indicate that c-FLIP is required for breast cancer growth and is a relevant therapeutic target for the treatment of breast cancer.
Department of Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Travis W
TW
Day
Anthony L
AL
Sinn
Su
S
Huang
Karen E
KE
Pollok
George E
GE
Sandusky
Ahmad R
AR
Safa
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D034741:RNA, Small Interfering / Q000235:genetics; D017154:Stromal Cells / Q000473:pathology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D034741:RNA, Small Interfering