Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer

被引:56
作者
Barboro, P. [1 ]
Repaci, E. [1 ]
Rubagotti, A. [1 ,2 ]
Salvi, S. [1 ]
Boccardo, S. [1 ]
Spina, B. [1 ]
Truini, M. [1 ]
Introini, C. [1 ]
Puppo, P. [1 ]
Ferrari, N. [1 ]
Carmignani, G. [3 ]
Boccardo, F. [1 ,2 ]
Balbi, C. [1 ]
机构
[1] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[2] Univ Genoa, Dipartimento Oncol Biol & Genet, I-16132 Genoa, Italy
[3] Univ Genoa, Dipartimento Urol, I-16132 Genoa, Italy
关键词
heterogeneous nuclear ribonucleoprotein K; prostate cancer; nuclear matrix; immunohistochemistry; western blot; biological markers; HNRNP-K; MATRIX PROTEINS; PROTEOMIC ANALYSIS; ANDROGEN RECEPTOR; CELLS; PHOSPHORYLATION; DIFFERENTIATION; OVEREXPRESSION; CARCINOGENESIS; IDENTIFICATION;
D O I
10.1038/sj.bjc.6605057
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 antiandrogen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa. British Journal of Cancer (2009) 100, 1608-1616. doi: 10.1038/sj.bjc.6605057 www.bjcancer.com Published online 28 April 2009 (C) 2009 Cancer Research UK
引用
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页码:1608 / 1616
页数:9
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