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 cons...

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Bibliographic Details
Published in:Molecular carcinogenesis 2016-11, Vol.55 (11), p.1667-1677
Main Authors: Hatziieremia, Sophia, Mohammed, Zahra, McCall, Pamela, Willder, Jennifer M., Roseweir, Antonia K., Underwood, Mark A., Edwards, Joanne
Format: Article
Language:English
Subjects:
androgen receptor
Cell Line, Tumor
Cell Survival
Cellular biology
Down-Regulation
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Male
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - metabolism
Neoplasm Recurrence, Local - pathology
Prognosis
prognostic biomarker
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Receptors, Androgen - metabolism
Signal transduction
STAT1 Transcription Factor - genetics
STAT1 Transcription Factor - metabolism
Survival Analysis
Transcription factors
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Summary: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 
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22417