BACKGROUND: Cell line models suggest that activation of NFκB is associated with progression of prostate cancer.
This pathway may be a therapeutic target if these observations translate to clinical specimens.
METHODS: Immunohistochemistry measured NFκBp65 (p65), NFκBp65 nuclear localisation signal (NLS), NFκBp65 phosphorylated at ser 276 (p65ser276), NFκBp65 phosphorylated at ser 536 (p65ser536), IκBα phosphorylated at ser 32/36 (pIκBαser32/36) 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 NFκB inhibition in prostate carcinogenesis.
RESULTS: In HNPC tumours, NLS expression significantly associated with a shorter time to disease recurrence and disease-specific death. In CRPC tumours p65, pIκBαser32/36) and MMP-9 expression significantly associated with shorter time to death from disease recurrence and shorter disease-specific death. MMP-9 and pIκBαser32/36) 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 NFκB in LNCaP cells significantly reduced cellular proliferation and induced apoptosis.
CONCLUSION: These results provide further evidence that the NFκB pathway could be exploited as a target for CRPC.
Written by:
McCall P, Bennett L, Ahmad I, Mackenzie LM, Forbes IW, Leung HY, Sansom OJ, Orange C, Seywright M, Underwood MA, Edwards J. Are you the author?
Unit of Experimental therapeutics, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ UK.
Reference: Br J Cancer. 2012 Oct 23;107(9):1554-63.
doi: 10.1038/bjc.2012.372
PubMed Abstract
PMID: 23093296
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