title: Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer.
abstract: 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.
authors.affiliation: Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Sacca
authors.forename: R
authors.initials: R
authors.lastname: Meiss
authors.forename: G
authors.initials: G
authors.lastname: Casas
authors.forename: O
authors.initials: O
authors.lastname: Mazza
authors.forename: J C
authors.initials: JC
authors.lastname: Calvo
authors.forename: N
authors.initials: N
authors.lastname: Navone
authors.forename: E
authors.initials: E
authors.lastname: Vazquez
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured
chemical_list: D006427:Hemin; D051547:Heme Oxygenase-1