STAT1 loss has previously been implicated in cell line studies to modify prostate cancer cell growth and survival, however the clinical significance of this has not previously been established. This study investigated if STAT1 loss was associated with patient outcome measures and the phenotypic consequence of STAT1 silencing.
STAT1 expression was assessed in two patient cohorts with localised (n = 78) and advanced prostate cancer at initial diagnosis (n = 39) by immunohistochemistry (IHC). Impact of STAT1 silencing on prostate cancer cells lines was assessed using Cell Death detection ELISA, TLDA gene signature apoptosis arrays, WST-1 assay, xCELLigence system, clonogenic assay, and wound healing assay. In the localised patient cohort, low expression of STAT1 was associated with shorter time to disease recurrence (3. 8 vs 7. 3 years, P = 0. 02) and disease specific survival (6. 6 vs 9. 3 years, P = 0. 05). In the advanced patient cohort, low expression was associated with shorter time to disease recurrence (2. 0 vs 3. 9 years, P = 0. 001). When STAT1 was silenced in PC3 cells (AR negative) and LNCaP cells (AR positive) silencing did not influence levels of apoptosis in either cell line and had little effect on cell viability in the LNCaP cells. In contrast, STAT1 silencing in the PC3 cells resulted in a pronounced increase in cell viability (WST-1 assay: mock silenced vs STAT1 silenced, P < 0. 001), clonagenicity (clonogenic assay: mock silenced vs STAT1 silenced, P < 0. 001), and migration (wound healing: mock silenced vs STAT1 silenced, P < 0. 001). In conclusion, loss of STAT1 may promote prostate cancer recurrence in AR negative patients via increasing cell viability. © 2015 Wiley Periodicals, Inc.
Molecular carcinogenesis. 2015 Oct 23 [Epub ahead of print]
Sophia Hatziieremia, Zahra Mohammed, Pamela McCall, Jennifer M Willder, Antonia K Roseweir, Mark A Underwood, Joanne Edwards
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. , Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. , Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. , Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. , Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. , Department of Urology, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom. , Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.