title: Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells.
abstract: In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SK-BR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neu-overexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses.
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, J. W. Goethe University, Theodor-Stern-Kai 7, Frankfurt 60590, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Faltus
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
authors.forename: Brigitte
authors.initials: B
authors.lastname: Zimmer
authors.forename: Andrea
authors.initials: A
authors.lastname: Krämer
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhardt
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering
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