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PTEN deletion and heme oxygenase-1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome.
Li, Yunru; Su, Jie; DingZhang, Xiao; Zhang, Jianguo; Yoshimoto, Maisa; Liu, Shuhong; Bijian, Krikor; Gupta, Ajay; Squire, Jeremy A; Alaoui Jamali, Moulay A; Bismar, Tarek A.
Afiliação
  • Li Y; Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
J Pathol ; 224(1): 90-100, 2011 May.
Article em En | MEDLINE | ID: mdl-21381033
Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Biomarcadores Tumorais / PTEN Fosfo-Hidrolase / Heme Oxigenase-1 Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Animals / Humans / Male / Middle aged Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Biomarcadores Tumorais / PTEN Fosfo-Hidrolase / Heme Oxigenase-1 Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Animals / Humans / Male / Middle aged Idioma: En Ano de publicação: 2011 Tipo de documento: Article