title: 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.
abstract: 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.
authors: From the McArdle Laboratory for Cancer Research and.
authors: Saja A
authors: SA
authors: Fakhraldeen
authors: From the McArdle Laboratory for Cancer Research and.
authors: Rod J
authors: RJ
authors: Clark
authors: the Departments of Neuroscience.
authors: Avtar
authors: A
authors: Roopra
authors: From the McArdle Laboratory for Cancer Research and.
authors: Emily N
authors: EN
authors: Chin
authors: Pathology and Laboratory Medicine.
authors: Wei
authors: W
authors: Huang
authors: the School of Natural Sciences, Hampshire College, Amherst, Massachusetts 01002.
authors: John
authors: J
authors: Castorino
authors: Medicine, and.
authors: Kari B
authors: KB
authors: Wisinski
authors: Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705-2276 and.
authors: TaeWon
authors: T
authors: Kim
authors: Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705-2276 and.
authors: Vladimir S
authors: VS
authors: Spiegelman
authors: From the McArdle Laboratory for Cancer Research and alexander@oncology.wisc.edu.
authors: Caroline M
authors: CM
authors: Alexander
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008875:Middle Aged; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: C519161:CRD-BP protein, mouse; C406144:IGF2BP1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: IMP1; RNA binding protein; RNA metabolism; RNA-protein interaction; alternate transcription site; breast cancer; clonogenicity; mRNA; mammary gland; multifunctional protein