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Cold‐inducible RNA binding protein modulates proliferation in the mouse mammary epithelium
Author(s) -
Hartley Rebecca S,
Mitchell Therese,
Guo Xun,
Wu Yuehan,
Brandt Yekaterina,
Hathaway Helen J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.494.2
Subject(s) - mammary gland , biology , cyclin d1 , lactation , epithelium , downregulation and upregulation , genetically modified mouse , cell growth , transgene , messenger rna , cyclin b1 , cancer research , microbiology and biotechnology , cell cycle , apoptosis , breast cancer , cancer , gene , pregnancy , cyclin dependent kinase 1 , biochemistry , genetics
Cold‐inducible RNA binding protein (CIRP) is upregulated in response to cellular stress, either facilitating or repressing translation of its mRNA targets. We showed that CIRP is upregulated in all breast cancer cell lines examined, while others have shown CIRP overexpression in primary breast tumors. In the MCF‐7 breast cancer cell line, CIRP upregulates the expression of another stress‐induced RNA binding protein, HuR, as well as the cell cycle regulator cyclin E1. Both HuR and cyclin E1 are also overexpressed in breast cancer, with higher expression correlating with a poor prognosis. In order to determine the in vivo function of CIRP in the breast epithelium, we produced a transgenic mouse expressing CIRP in the mammary epithelium under control of the mouse mammary tumor virus (MMTV) regulatory sequences. Real‐time RT‐PCR showed maximal expression of the transgene in the pregnant mouse at gestation day 16, and a second peak of expression after birth, at lactation day 14. Immunohistochemistry for the proliferation marker Ki‐67 showed decreased proliferation in the mammary epithelium of CIRP transgenic mice compared to wild type littermates at gestation day 16 (45% CIRP vs. 56% wild type, p=0.05) and lactation day 1 (7% CIRP vs. 25% wild type, p=0.0068). These results suggest that CIRP negatively regulates proliferation in the intact mammary gland. We are currently examining effects of CIRP expression on apoptosis in the involuting mammary gland. This work was supported by a grant from the National Cancer Institute‐National Institutes of Health to RSH (R01CA095898).