Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells.

Autor:	Fakhraldeen SA; From the McArdle Laboratory for Cancer Research and., Clark RJ; From the McArdle Laboratory for Cancer Research and., Roopra A; the Departments of Neuroscience., Chin EN; From the McArdle Laboratory for Cancer Research and., Huang W; Pathology and Laboratory Medicine., Castorino J; the School of Natural Sciences, Hampshire College, Amherst, Massachusetts 01002., Wisinski KB; Medicine, and., Kim T; Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705-2276 and., Spiegelman VS; Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705-2276 and., Alexander CM; From the McArdle Laboratory for Cancer Research and alexander@oncology.wisc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 May 22; Vol. 290 (21), pp. 13386-400. Date of Electronic Publication: 2015 Apr 10.
DOI:	10.1074/jbc.M115.655175
Abstrakt:	CRD-BP/IGF2BP1 has been characterized as an "oncofetal" RNA binding protein typically highly expressed in embryonic tissues, suppressed in normal adult tissues, but induced in many tumor types. In this study, we show that adult breast tissues express ubiquitous but low levels of CRD-BP protein and mRNA. Although CRD-BP mRNA expression is induced in breast tumor cells, levels remain ∼1000-fold lower than in embryonic tissues. Despite low expression levels, CRD-BP is required for clonogenic growth of breast cancer cells. We reveal that because the most common protein isoform in normal adult breast and breast tumors has an N-terminal deletion (lacking two RNA recognition motif (RRM) domains) and is therefore missing antibody epitopes, CRD-BP expression has been under-reported by previous studies. We show that a CRD-BP mutant mouse strain retains expression of the shorter transcript (ΔN-CRD-BP), which originates in intron 2, suggesting that the impact of complete ablation of this gene in mice is not yet known. Either the full-length CRD-BP or the N-terminally truncated version can rescue the clonogenicity of CRD-BP knockdown breast cancer cells, suggesting that clonogenic function is served by either CRD-BP isoform. In summary, although CRD-BP expression levels are low in breast cancer cells, this protein is necessary for clonogenic activity. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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