Evaluation of the in vivo role of Cold‐Inducible RNA Binding Protein (CIRP) in breast development and disease

RNA binding proteins (RBPs) post‐transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions (UTRs) of mRNAs. For example, cold‐inducible RBP (CIRP) is expressed during normal breast development and overexpressed in breast cancer. In vitro studies have shown that CIRP promotes cell proliferation and survival. This study seeks to determine the in vivo role of CIRP in breast development and in breast cancer. We generated a transgenic mouse that expresses human CIRP in the mammary epithelium under control of the MMTV‐LTR. Mammary gland morphology, proliferation, and apoptosis were assessed at key developmental time points: puberty, pregnancy, lactation and weaning. While there were no differences in morphology or apoptosis between mammary glands from CIRP and wild type mice, there was significantly less proliferation in CIRP mammary glands at lactation day one, a time when proliferation is normally decreasing. This result suggests a potential role for CIRP in suppressing proliferation at specific developmental time points. We next assessed the effect(s) of CIRP overexpression on breast tumorigenesis in vivo by crossing a mouse model of breast cancer (PyMT) with CIRP mice. CIRP/PyMT mammary glands had fewer mammary intraepithelial neoplasias as compared to the PyMT mammary glands. Contrary to previous in vitro studies, our data suggests that CIRP inhibits proliferation and impedes tumorigenesis. This research was supported by the Initiatives to Maximize Student Development (IMSD) program at the University of New Mexico and the Dedicated Health Research Fund from the University of New Mexico SOM.