V体育ios版 - NF魏B signalling is upregulated in a subset of castrate-resistant prostate cancer patients and correlates with disease progression

Abstract

background:聽聽Cell line models suggest that activation of NF魏B is associated with progression of prostate cancer. This pathway may be a therapeutic target if these observations translate to clinical specimens.

methods:聽聽Immunohistochemistry measured NF魏Bp65 (p65), NF魏Bp65 nuclear localisation signal (NLS), NF魏Bp65 phosphorylated at ser 276 (p65ser276), NF魏Bp65 phosphorylated at ser 536 (p65ser536), I魏B伪 phosphorylated at ser 32/36 (pI魏B伪ser32/36) and MMP-9 protein expression in 61 matched hormone naive prostate cancer (HNPC) and castrate-resistant prostate cancer (CRPC) tumours. Animal and cell models were used to investigate the role of NF魏B inhibition in prostate carcinogenesis.

results:聽聽In HNPC tumours, NLS expression significantly associated with a shorter time to disease recurrence and disease-specific death. In CRPC tumours p65, pI魏B伪ser32/36 and MMP-9 expression significantly associated with shorter time to death from disease recurrence and shorter disease-specific death. MMP-9 and pI魏B伪ser32/36 expression significantly associated with metastases at recurrence and were independent of Gleason sum and prostate-specific antigen at recurrence. Expression of phosphorylated Akt was associated with increased p65 activation in mouse models and inhibition of NF魏B in LNCaP cells significantly reduced cellular proliferation and induced apoptosis VSports app下载.

conclusion:聽聽These results provide further evidence that the NF魏B pathway could be exploited as a target for CRPC.