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Overexpression of an mRNA-binding protein in human colorectal cancer

Abstract

A Coding Region instability Determinant-Binding Protein (CRD-BP) binds in vitro to c-myc mRNA and appears to stabilize the mRNA. The CRD-BP gene is amplified in one-third of human breast cancer cases, and the CRD-BP appears to be an oncofetal protein. To analyse CRD-BP expression in human cancer tissue, paired extracts of cancer and normal colon specimens from 21 patients were analysed by immunoblotting and/or reverse transcriptase-polymerase chain reaction. Seventeen cancer specimens out of 21 (81%) were positive for CRD-BP expression by one or both assays. With one exception, normal colon specimens were negative for CRD-BP expression; specimens of inflammatory bowel and a villous adenoma also had no detectable CRD-BP. The lack of CRD-BP expression in normal colon did not result from indiscriminate protein or RNA degradation. c-myc mRNA levels appeared to be elevated in tumor specimens. We conclude that the CRD-BP is scarce or absent from normal colon but is overexpressed in colorectal cancer. The CRD-BP might be a novel human tumor marker.

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Abbreviations

CRD:

c-myc mRNA coding region instability determinant

CRD-BP:

c-myc mRNA coding region instability determinant-binding protein

CHTN:

Cooperative Human Tissue Network

RT–PCR:

reverse transcriptase-polymerase chain reaction

RNP:

ribonucleoprotein

RGG:

arginine-glycine-glycine RNA-binding domain homology domain

HRP:

horseradish peroxidase

GAPDH:

glyceraldehyde phosphate dehydrogenase

CEA:

carcinoembryonic antigen

PSA:

prostate-specific antigen

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Acknowledgements

We thank Charles Tessier for helpful suggestions and encouragement and the Cooperative Human Tissue Network (CHTN) for providing tissue specimens. The CHTN is funded by the National Cancer Institute. We greatly appreciate the assistance of Jim Davoli at the CHTN. This work was supported by NCI grants R01-CA78710 (J Ross) and P30-CA-07175 (CCSG to the McArdle Laboratory) and by a grant from the University of Wisconsin Robert Draper Technology Innovation Fund (J Ross).

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Correspondence to Jeffrey Ross.

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Ross, J., Lemm, I. & Berberet, B. Overexpression of an mRNA-binding protein in human colorectal cancer. Oncogene 20, 6544–6550 (2001). https://doi.org/10.1038/sj.onc.1204838

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