6533b82dfe1ef96bd1291da6

RESEARCH PRODUCT

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.

Jehad CharoRolf KiesslingSunil K. ParapuramRichard C. HuntBarbara SeligerD. Margaret HuntAniruddha Choudhury

subject

Cancer Researchmedicine.medical_specialtySmall interfering RNAApoptosisBreast NeoplasmsAntibodies Monoclonal HumanizedTransfectionHER2/neuGene productRNA interferenceInternal medicineCell Line TumormedicineGene silencingHumansGene SilencingRNA Small Interferingskin and connective tissue diseasesneoplasmsOvarian NeoplasmsMessenger RNAbiologyHistocompatibility Antigens Class IRNAAntibodies MonoclonalTransfectionGenes erbB-2TrastuzumabUp-RegulationEndocrinologyOncologyCancer researchbiology.proteinFemale

description

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 G(1)/S-phase. Our results suggest that siRNA may be an effective method of abrogating the effect of HER2 in tumorigenesis.

10.1002/ijc.11497https://pubmed.ncbi.nlm.nih.gov/14618618