SMALL INTERFERING RNA (siRNA) INHIBITS THE EXPRESSION OF THE Her2/Neu GENE, UPREGULATES HLA CLASS I AND INDUCES APOPTOSIS OF Her2/Neu POSITIVE TUMOR CELL LINES

SMALL INTERFERING RNA (siRNA) INHIBITS THE EXPRESSION OF THE Her2/Neu GENE, UPREGULATES HLA CLASS I AND INDUCES APOPTOSIS OF Her2/Neu POSITIVE TUMOR CELL LINES

SMALL INTERFERING RNA (siRNA) INHIBITS THE EXPRESSION OF THE Her2/Neu GENE, UPREGULATES HLA CLASS I AND INDUCES APOPTOSIS OF Her2/Neu POSITIVE TUMOR CELL LINES

Silencing of a specific mRNA using double stranded RNA oligonucleotides represents one of the newest technologies
for suppressing a specific gene product. Small interfering RNA (siRNA) are 21 nucleotides long, double stranded RNA
fragments that are identical in sequence to the target mRNA. We designed 3 such siRNA against the Her2/neu (HER2) gene. The HER2 gene is known to play an important role in the oncogenesis of several types of cancers, such as breast, ovarian, colon and gastric cancers. Introduction of the siRNA into HER2 positive tumor lines in vitro greatly reduced
the cell surface expression of the HER2 protein. Concurrently, a range of effects on cell physiology, such as growth
inhibition or apoptosis, was observed. The expression of HLA class I was observed to be upregulated when HER2 was
silenced with siRNA. Treatment of SKBr3 and MCF7/HER2 tumor cell lines with the HER2 siRNA resulted in growth arrest of cells in the late G1/S-phase. Our results suggest thatsiRNA may be an effective method of abrogating the effect of HER2 in tumorigenesis.
© 2003 Wiley-Liss, Inc.
Key words: siRNA; Her-2/neu; RNAi; oncogene; breast cancer

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