Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer.
Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with pleiotropic functions, was differentially expressed in prostate cancer (PCa) tissues. This study aimed to characterise the expression of hnRNP K and its subcellular localisation in PCa, utilising immunohistochemical and quantitative western blot techniques. Furthermore, the hnRNP K expression was studied in human PCa cell lines in order to determine its modulation by bicalutamide, the anti-androgen widely used in PCa therapy. Immunohistochemical staining of paraffin-embedded tissues showed that hnRNP K was overexpressed in PCa, where it was localised both in the cytoplasm and in the nucleus. Staining of non-tumour tissues showed exclusively nuclear localisation and a less intense or absent signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was higher in PCa compared with non-tumour tissues and closely correlated with Gleason score (P=0.008). Higher expression within the NM was significantly (P=0.032) associated with poor prognosis. In two-dimensional western blot analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most differently expressed between non-tumour and PCa tissues. Preliminary results indicate that hnRNP K can be modulated in vitro by a non-steroidal anti-androgen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa.
Barboro
P
P
Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, Genova, Italy.
Repaci
E
E
Rubagotti
A
A
Salvi
S
S
Boccardo
S
S
Spina
B
B
Truini
M
M
Introini
C
C
Puppo
P
P
Ferrari
N
N
Carmignani
G
G
Boccardo
F
F
Balbi
C
C
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D011494:Protein Kinases