Effects of siRNA-mediated Silencing of ERBB2, IGF-1R, and ITGB1 in HER2-positive Breast Cancer Cells.

BACKGROUND/AIM: One of the hallmarks of cancer is deregulation of multiple signaling pathways, which can lead to uncontrolled proliferation and migration of cells. Over-expression and mutations in human epidermal growth factor receptor 2 (HER2) can lead to overactivation of these pathways, potentially developing cancer in different tissues, including breast tissue. IGF-1R and ITGB-1 are two receptors that have been linked to cancer development. Therefore, the aim of this study was to investigate the effects of silencing of the corresponding genes using specific siRNAs.

MATERIALS AND METHODS

Transient silencing of HER2, ITGB-1, and IGF-1R was conducted using siRNAs and expression was quantified by reverse transcription-quantitative polymerase chain reaction. Viability in human breast cancer cells SKBR3, MCF-7, and HCC1954 and cytotoxicity in HeLa cells were tested using WST-1 assay.

RESULTS

The use of anti-HER2 siRNAs in a breast cancer cell line over-expressing HER2 (SKBR3) led to a decrease in cell viability. However, silencing of ITGB-1 and IGF-1R in the same cell line had no significant effects. Silencing of any of the genes encoding any of the three receptors in MCF-7, HCC1954, and HeLa had no significant effects.

CONCLUSION

Our results provide evidence towards using siRNAs against HER2-positive breast cancer. Silencing of ITGB-1 and IGF-R1 did not significantly inhibit the growth of SKBR3 cells. Therefore, there is need for testing the effect of silencing ITGB-1 and IGF-R1 in other cancer cell lines over-expressing these biomarkers and explore their potential use in cancer therapy.