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British Journal of Cancer (2007) 97, 1683-1689.
doi:10.1038/sj.bjc.6604081 www.bjcancer.com Published online 20 November 2007
Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer
P Sacca1, R Meiss2, G Casas3, O Mazza4, J C Calvo1,5, N Navone6 and E Vazquez5
1Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
2Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Pacheco de Melo 3081, Buenos Aires 1425, Argentina
3Departamento de Patología, Hospital Alemán, Buenos Aires, Argentina
4Servicio Urología, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina
5Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, CONICET, Pabellón II, 4to Piso, Buenos Aires 1428, Argentina
6Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence to: Professor Dr E Vazquez, Intendente Güiraldes 2160, Ciudad Universitaria, Pab II, 4to piso, Buenos Aires 1428, Argentina; E-mail: elba@qb.fcen.uba.ar
Received 29 June 2007; revised 10 October 2007; accepted 12 October 2007; published online 20 November 2007
The role of oxidative stress in prostate cancer has been increasingly recognised. Acute and chronic inflammations generate reactive oxygen species that result in damage to cellular structures. Haeme oxygenase-1 (HO-1) has cytoprotective effects against oxidative damage. We hypothesise that modulation of HO-1 expression may be involved in the process of prostate carcinogenesis and prostate cancer progression. We thus studied HO-1 expression and localisation in 85 samples of organ-confined primary prostate cancer obtained via radical prostatectomy (Gleason grades 4-9) and in 39 specimens of benign prostatic hyperplasia (BPH). We assessed HO-1 expression by immunohistochemical staining. No significant difference was observed in the cytoplasmic positive reactivity among tumours (84%), non-neoplastic surrounding parenchyma (89%), or BPH samples (87%) (P=0.53). Haeme oxygenase-1 immunostaining was detected in the nuclei of prostate cancer cells in 55 of 85 (65%) patients but less often in non-neoplastic surrounding parenchyma (30 of 85, 35%) or in BPH (9 of 39, 23%) (P<0.0001). Immunocytochemical and western blot analysis showed HO-1 only in the cytoplasmic compartment of PC3 and LNCaP prostate cancer cell lines. Treatment with hemin, a well-known specific inducer of HO-1, led to clear nuclear localisation of HO-1 in both cell lines and highly induced HO-1 expression in both cellular compartments. These findings have demonstrated, for the first time, that HO-1 expression and nuclear localisation can define a new subgroup of prostate cancer primary tumours and that the modulation of HO-1 expression and its nuclear translocation could represent new avenues for therapy.
Keywords: haeme oxygenase-1; prostate cancer; nuclear localisation; oxidative stress
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| Print ISSN: 0007-0920 | Online ISSN: 1532-1827 | © 2007 Cancer Research UK | ||
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