EVALUATION OF THE IN VIVO ROLE OF A COLD-INDUCIBLE RNA BINDING PROTEIN (CIRP)
Daniel Lujan1, Selina Garcia2, Rebecca S. Hartley3.
1University of New Mexico Health Sciences Center, Albuquerque, NM, 2University of New Mexico, Albuquerque, NM, 3University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM.
RNA binding proteins (RBPs) post-transcriptionally regulate gene expression at the mRNA level. Many RBPs associate with the regulatory sequences in the 5â€™ and 3â€™ untranslated regions of mRNA encoding, cancer-associated genes, increasing their expression. Furthermore, dysfunction of several RBPs is associated with cancer: they regulate target genes that promote cell growth, survival, and proliferation. Our current knowledge of RBPs and their role in regulating cancer-associated genes is largely based on in vitro studies. Our current study seeks to determine the in vivo role of cold-inducible RBP (CIRP) that is overexpressed in breast cancer. In cultured cells, CIRP promotes cell proliferation and survival, both hallmarks of cancer. Using mice expressing the human CIRP (hCIRP) transgene in the mammary epithelium, we compared proliferation and apoptosis during mammary gland development between wild-type mice and hCIRP mice. CIRPâ€™s effects on mammary tumor growth were also assessed using double-transgenic hCIRP/PyMT mice. Mice expressing Polyoma virus middle T antigen (PyMT) in the mammary epithelium develop tumors by 7 weeks of age. Contrary to previous in vitro studies, our current data suggests that CIRP inhibits proliferation and slows tumor growth. These data may provide us with a more precise understanding of the in vivo function of CIRP.