Silencing of CXCR4 blocks breast cancer metastasis.
RNA interference technology, silencing targeted genes in mammalian cells, has become a powerful tool for studying gene function. For the first time in cancer research, we show that direct injection of a pool of naked small interfering RNA (siRNA) duplexes can prevent tumorigenesis in an animal model, suggesting a novel preventive and therapeutic strategy for cancer management. As a model system, we used siRNA duplexes of CXCR4 to block breast cancer metastasis. Here, we show that blocking CXCR4 expression at the mRNA level by a combination of two siRNAs impairs invasion of breast cancer cells in Matrigel invasion assay and inhibits breast cancer metastasis in an animal model. Targeting more than one site of the target gene may be important to overcome the functional redundancy of other variants of a single gene, especially in in vivo experiments. Moreover, our studies confirm the necessity of CXCR4 in breast cancer metastasis.
Liang
Zhongxing
Z
Department of Hematology/Oncology, Winship Cancer Institute, Emory University, 1701 Uppergate Drive, Atlanta, GA 30322, USA.
Yoon
Younghyoun
Y
Votaw
John
J
Goodman
Mark M
MM
Williams
Larry
L
Shim
Hyunsuk
H
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4