TY  - JOUR
A1  - Faltus, Timo
A1  - Yuan, Juping
A1  - Zimmer, Brigitte
A1  - Krämer, Andrea
A1  - Loibl, Sibylle
A1  - Kaufmann, Manfred
A1  - Strebhardt, Klaus
T1  - Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells
T2  - Neoplasia
N2  - 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.
KW  - HER2/neu
KW  - RNA interference
KW  - siRNA
KW  - antiproliferative activity
KW  - apoptosis
Y1  - 2004
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45309
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-453099
SN  - 1476-5586
SN  - 1522-8002
N1  - Under a Creative Commons license
VL  - 6
IS  - 6
SP  - 786
EP  - 795
PB  - Stockton Press
CY  - Basingstoke
ER  -