Loss of signal transducer and activator of transcription 1 is associated with prostate cancer recurrence.
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.
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Sophia
S
Hatziieremia
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Zahra
Z
Mohammed
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Pamela
P
McCall
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Jennifer M
JM
Willder
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Antonia K
AK
Roseweir
Department of Urology, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom.
Mark A
MA
Underwood
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. J.Edwards@glasgow.ac.uk.
Joanne
J
Edwards
D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis
C410798:AR protein, human; D011944:Receptors, Androgen; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human
androgen receptor; prognostic biomarker; signal transduction