Abstract A64: Cold-inducible RNA binding protein (CIRP) links inflammation and breast cancer

Abstract

Abstract RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with the regulatory sequences in the untranslated regions of mRNAs. RBPs are often disrupted in cancer, but current knowledge of their role in regulating cancer-associated genes is largely based on in vitro studies. This study seeks to determine the in vivo role of cold-inducible RBP (CIRP), which is overexpressed in some human breast cancers. CIRP promotes cell proliferation and survival and inhibits apoptosis in vitro, as well as promotes inflammation in vivo, all hallmarks of cancer. We set out to test the hypothesis that CIRP promotes breast tumorigenesis in vivo by crossing a transgenic mouse overexpressing CIRP in the mammary epithelium with the PyMT mouse model of breast cancer. Effects on both early (7 weeks of age) and late (14 weeks) tumorigenesis were assessed. Unexpectedly, mammary glands from 7-week CIRP/PyMT mice had 50% fewer mammary intraepithelial neoplasias than those from PyMT mice. Consistent with this, histopathologic analysis showed decreased mitosis and increased apoptosis in CIRP/PyMT vs. PyMT mammary glands. Late-stage tumorigenesis was also inhibited. CIRP/PyMT mice had slower tumor growth kinetics, smaller tumors, decreased tumor burden, and decreased pulmonary metastasis compared to PyMT mice. To assess mechanism, mammary glands from 7- and 14-week mice were incubated in medium overnight followed by Luminex cytokine assays on the medium. Results showed a decrease in cytokines that promote inflammation, angiogenesis, and metastasis. Altogether, results suggest that in vivo, CIRP inhibits proliferation and promotes apoptosis to suppress early tumorigenesis, potentially via decreasing the protumorigenic inflammatory response. Citation Format: Daniel Albino Lujan, Nora Perrone-Bizzozero, Ellen J. Beswick, Donna F. Kusewitt, Rebecca S. Hartley. Cold-inducible RNA binding protein (CIRP) links inflammation and breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A64.