Abstract 4346: Influence of ionizing radiation on transcription of human endogenous retrovirus-K (HERV-K) in breast cancer cell lines

Abstract

Abstract Ionizing Radiation (IR) has been reported to increase the transcriptional activity of many viruses, including retroviruses. We hypothesized that IR could reactivate subsets of Human Endogenous Retroviruses (HERVs), which are retroviruses integrated into the human genome, remnants of ancient retroviral infections, and that HERV-derived peptides, the final product of HERVs transcription, will increase the diversity of the antigen repertoire presented by irradiated cancer cells, thereby inducing anti-tumor immune responses. IR has been shown to increase the immunogenicity of cancer cells by modulating various cellular processes, including antigen presentation by MHC. HERVs are known to be transcribed in numerous diseases including cancer, HIV infection, and autoimmune disorders. HERV-K is the most recently integrated and thus intact HERV family, with approximately 350 loci in the human genome, 98 to 99% identical. Previous experiments in our laboratory have shown IR-dependent increases in HERV-K transcription, plus increased HERV-K-derived peptides in irradiated prostate carcinoma cell lines upon proteomic LC-MS/MS analysis of peptides eluted from MHC-I complexes. HERV-K activation has been reported in breast cancer. To test the influence of IR on HERV-K transcription, three breast cancer cell lines (MDA-MB-468, MDA-MB-231 and MCF7) were analyzed by RT-PCR and qRT-PCR at specific time-points, from 1 to 72 hours, after different doses of α-irradiation (0, 2.5, 5, 10 and 20 Gy). HERV-K transcription was detected in all cell lines studied. After IR, each cell line showed distinct dose-response curves of HERV-K transcription during the time-frame of observation. Overall, the peak of HERV-K transcription in irradiated samples, when compared to non-irradiated samples, was increased by an average of 2- to 5-fold. Multiple, active, individual HERV-K loci were detected. Cloning and sequencing are ongoing to identify specific active loci for each cell line. These findings show that HERV-K is actively transcribed in breast carcinoma cell lines. The IR-dependent increase in HERV-K transcription may enhance antigen repertoire diversity, contribute to the immunomodulatory properties of IR, and offers attractive targets for the development of novel IR-enhanced immunotherapies for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4346. doi:1538-7445.AM2012-4346