title: Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer.
abstract: Heterogeneous ribonucleoprotein K (hnRNP K) is a member of the hnRNP family which has several different cellular roles including transcription, mRNA shuttling, RNA editing and translation. Several reports implicate hnRNP K having a role in tumorigenesis, for instance hnRNP K increases transcription of the oncogene c-myc and hnRNP K expression is regulated by the p53/MDM 2 pathway. In this study comparing normal colon to colorectal cancer by proteomics, hnRNP K was identified as being overexpressed in this type of cancer. Immunohistochemistry with a monoclonal antibody to hnRNP K (which we developed) on colorectal cancer tissue microarray, confirmed that hnRNP K was overexpressed in colorectal cancer (P<0.001) and also showed that hnRNP K had an aberrant subcellular localisation in cancer cells. In normal colon hnRNP K was exclusively nuclear whereas in colorectal cancer the protein localised both in the cytoplasm and the nucleus. There were significant increases in both nuclear (P=0.007) and cytoplasmic (P=0.001) expression of hnRNP K in Dukes C tumours compared with early stage tumours. In Dukes C patient's good survival was associated with increased hnRNP K nuclear expression (P=0.0093). To elaborate on the recent observation that hnRNP K is regulated by p53, the expression profiles of these two proteins were also analysed. There was no correlation between hnRNP K and p53 expression, however, patients who presented tumours that were positive for hnRNP K and p53 had a poorer survival outcome (P=0.045).
authors.affiliation: Department of Pathology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. b.carpenter@auvation.com
authors.forename: B
authors.initials: B
authors.lastname: Carpenter
authors.forename: M
authors.initials: M
authors.lastname: McKay
authors.forename: S R
authors.initials: SR
authors.lastname: Dundas
authors.forename: L C
authors.initials: LC
authors.lastname: Lawrie
authors.forename: C
authors.initials: C
authors.lastname: Telfer
authors.forename: G I
authors.initials: GI
authors.lastname: Murray
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012261:Ribonucleoproteins / Q000096:biosynthesis*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human