RESUMO
BACKGROUND: We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA). METHODS: The effect of NRBP1 expression on tumor cell growth was analyzed by using RNAi. NRBP1 protein expression was evaluated on two TMAs containing prostate samples from more than 1,000 patients. Associations with clinico-pathological features, the proliferation marker Ki67 and survival data were analyzed. RESULTS: RNAi mediated silencing of NRBP1 expression in prostate cancer cell lines resulted in reduced cell growth (P < 0.05). TMA analysis revealed NRBP1 protein expression in benign prostate hyperplasia in 6% as compared to 60% in both, high-grade intraepithelial neoplasia and prostate cancer samples. Strong NRBP1 protein expression was restricted to prostate cancer and correlated with higher expression of the proliferation marker Ki67 (P < 0.05). Further, patients with strong NRBP1 protein expression showed poor clinical outcomes (P < 0.05). Analysis of matched localized cancer tissues before and after castration revealed that post-therapy-related repression of NRBP1 expression was significantly associated with better overall survival. CONCLUSIONS: We demonstrate that expression of NRBP1 is up-regulated during the progression of prostate cancer and that high NRBP1 expression is linked with poor prognosis and enhanced tumor cell growth.
Assuntos
Adenocarcinoma/patologia , Expressão Gênica , Neoplasias da Próstata/patologia , Receptores Citoplasmáticos e Nucleares/genética , Proteínas de Transporte Vesicular/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Finlândia/epidemiologia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Taxa de Sobrevida , Suíça/epidemiologia , Análise Serial de Tecidos , Proteínas de Transporte Vesicular/metabolismoRESUMO
Castration-resistant prostate cancer is the second most common cause of cancer death and results in a median survival of less than 2 years. In prostate cancer, fusions between TMPRSS2 and ERG are common. The ERG rearrangement prevalence in local recurrent castration-resistant prostate cancer compared to distant metastatic prostate cancer is unknown. We investigated the frequency of ERG rearrangement in local recurrent castration-resistant prostate cancer compared to distant metastatic prostate cancer, and assessed for associations between androgen receptor (AR) amplification and ERG rearrangement status. Samples from 134 patients diagnosed with prostate cancer (84 local recurrent castration resistant prostate cancer, 55 distant metastatic prostate cancer) were assessed for their ERG rearrangement and AR amplification status by fluorescence in situ hybridization. Statistical analysis was performed using the χ (2) test. We found that the ERG rearrangement occurs at a significantly lower frequency in distant metastatic prostate cancer (25 %) than in local recurrent castration-resistant prostate cancer (45 %). The AR amplification frequencies were 45 and 35 % in local recurrent castration-resistant prostate cancer and distant metastatic prostate cancer, respectively. The ERG rearrangement occurred at a lower frequency in distant metastatic prostate cancer compared to local recurrent castration-resistant prostate cancer.