Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells
- 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 SKBR-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/neuoverexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as anti proliferative agents that display activity against neoplastic cells at very low doses.
Author: | Timo Faltus, Juping YuanORCiDGND, Brigitte Zimmer, Andrea KrämerORCiDGND, Sibylle LoiblORCiDGND, Manfred KaufmannGND, Klaus StrebhardtORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-453099 |
DOI: | https://doi.org/10.1593/neo.04313 |
ISSN: | 1476-5586 |
ISSN: | 1522-8002 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/15720805 |
Parent Title (English): | Neoplasia |
Publisher: | Stockton Press |
Place of publication: | Basingstoke |
Document Type: | Article |
Language: | English |
Year of Completion: | 2004 |
Year of first Publication: | 2004 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2018/01/02 |
Tag: | HER2/neu; RNA interference; antiproliferative activity; apoptosis; siRNA |
Volume: | 6 |
Issue: | 6 |
Page Number: | 10 |
First Page: | 786 |
Last Page: | 795 |
Note: | Under a Creative Commons license |
HeBIS-PPN: | 426736532 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0 |