Hatziieremia, S., Mohammed, Z., McCall, P., Willder, J. M., Roseweir, A. K. , Underwood, M. A. and Edwards, J. (2016) Loss of signal transducer and activator of transcription 1 is associated with prostate cancer recurrence. Molecular Carcinogenesis, 55(11), pp. 1667-1677. (doi: 10.1002/mc.22417) (PMID:26495772)
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116753.pdf - Accepted Version 1MB |
Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Underwood, Mr Mark and Roseweir, Dr Antonia and Edwards, Professor Joanne and McCall, Dr Pamela and Willder, Dr Jennifer and Mohammed, Dr Zahra and Hatziieremia, Dr Sophia |
| Authors: | Hatziieremia, S., Mohammed, Z., McCall, P., Willder, J. M., Roseweir, A. K., Underwood, M. A., and Edwards, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Molecular Carcinogenesis |
| Publisher: | Wiley |
| ISSN: | 0899-1987 |
| ISSN (Online): | 1098-2744 |
| Published Online: | 23 October 2015 |
| Copyright Holders: | Copyright © 2015 Wiley |
| First Published: | First published in Molecular Carcinogenesis 55(11): 1667-1677 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher. |
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