Innovative Strategies for Breast Cancer Immunotherapy
Annual rept. 1 Sep 2013-31 Aug 2014
SRI INTERNATIONAL MENLO PARK CA
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Antitumor effects of human endogenous retrovirus type K HERV-K specific short hairpin RNAs shRNAs were determined in vitro and in vivo. We observed expression of HERV-K in breast cancer BC and inhibition of BC cell proliferation and induction of apoptosis in BC cells treated with anti-HERV-K antibodies. Furthermore, significantly slower growth was observed in BC cells transfected with a shRNA targeting the HERV-K env mRNA shRNAenv compared with a shRNA targeting a scrambled RNA sequence shRNAc. Significantly reduced numbers of colonies formed in soft agar when HERV-K env was knocked down in BC cell lines, compared to treatment with shRNAc, and significantly reduced tumor sizes and weights were demonstrated in mice xenografted with MDA-MB-231, MDA-MB-435.eb1, and SKBR3 BC cells stably transfected with shRNAenv, compared to cells stably transfected with a shRNAc. Downregulation of HERV-K with its targeting shRNA caused an increase of BC cells in the S phase and a corresponding decrease of cells in the G1 or G2-M. HERV-K viral RNAs were found to be involved in BC tumorigenesis via effects on not only p53 signaling pathways, but also other major signaling pathways that play critically important roles in tumorigenesis.
- Medicine and Medical Research