Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer - PubMed (original) (raw)

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

P Sacca et al. Br J Cancer. 2007.

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.

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Figures

Figure 1

Figure 1

Immunohistochemical staining of HO-1 in human prostatic tissues. Representative findings of HO-1 immunoreactivity. (A and B) Nuclear/cytoplasmic staining in PCa samples. (C) Cytoplasmic staining of non-neoplastic parenchyma surrounding PCa with nuclear HO-1 exclusion. (C1) Negative nuclear/cytoplasmic staining in tumoral region of the same sample. (D) Papillar structure of BPH covered by HO-1-negative and HO-1-positive cells. Original magnification: × 40.

Figure 2

Figure 2

Immunohistochemical detection of HO-1 nuclear translocation induced by hemin. Cytoplasmic immunostaining in LNCaP (A) and PC3 (D) cells grown under control conditions. Positive nuclear staining in LNCaP (B and C) and PC3 (E–G) cells grown with hemin (20 μ

M)

during 22 h. Magnification: × 40 (A, B, D–G) and × 100 (C).

Figure 3

Figure 3

Hemin induces the nuclear translocation of HO-1 in LNCaP and PC3 cell lines. Western blot analysis of HO-1 (32 kDa) in nuclear and cytoplasmic fractions extracted from LNCaP and PC3 cells cultured with or without hemin (20 μ

M

) for 22 h. Equal loading of the samples was verified by the detection of _β_-tubulin (55 kDa) and laminin A/C (67 kDa).

References

    1. Alam J, Igarashi K, Immenschuh S, Shibahara S, Tyrrell RM (2004) Regulation of heme oxygenase-1 gene transcription: recent advances and highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase. Antioxid Redox Signal 6: 924–933 - PubMed
    1. Aydin A, Arsova-Sarafinovska Z, Sayal A, Eken A, Erdem O, Erten K, Ozgok Y, Dimovski A (2006) Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostatic hyperplasia. Clin Biochem 39: 176–179 - PubMed
    1. Berberat PO, Dambrauskas Z, Gulbinas A, Giese T, Giese N, Kunzli B, Autschbach F, Meuer S, Buchler MW, Friess H (2005) Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment. Clin Cancer Res 11: 3790–3798 - PubMed
    1. Busserolles J, Megias J, Terencio MC, Alcaraz MJ (2006) Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway. Int J Biochem Cell Biol 38: 1510–1517 - PubMed
    1. Caballero F, Meiss R, Gimenez A, Batlle A, Vazquez E (2004) Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis. Int J Exp Pathol 85: 213–222 - PMC - PubMed

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