| 1. |
- Hagman, Zandra, et al.
(författare)
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miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:8, s. 1668-1676
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Tidskriftsartikel (refereegranskat)abstract
- Background:The microRNA-205 (miR-205) has been shown to be deregulated in prostate cancer (PCa). Here we continue to investigate the prognostic and therapeutic potential of this microRNA.Methods:The expression of miR-205 is measured by qRT-PCR and in situ hybridisation in a well-documented PCa cohort. An AGO2-based RIP-Chip assay is used to identify targets that are verified with western blots, luciferase reporter assay, ELISA and immunohistochemistry.Results:The expression of miR-205 is inversely correlated to the occurrence of metastases and shortened overall survival, and is lower in castration-resistant PCa patients. The miR-205 expression is mainly localised to the basal cells of benign prostate tissues. Genes regulated by miR-205 are enriched in, for example, the MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We demonstrate binding of miR-205 to the 3'UTR of androgen receptor (AR) and decrease of both AR transcript and protein levels. This finding was corroborated in the patient cohort were miR-205 expression inversely correlated to AR immunostaining in malignant prostate cells and to serum levels of prostate-specific antigen, an androgen-regulated protein.Conclusion:Taken together, these findings imply that miR-205 might have therapeutic potential, especially for the castration resistant and currently untreatable form of PCa.British Journal of Cancer advance online publication, 9 April 2013; doi:10.1038/bjc.2013.131 www.bjcancer.com.
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| 2. |
- Hagman, Zandra, et al.
(författare)
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The tumour suppressor miR-34c targets MET in prostate cancer cells.
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 109:5, s. 1271-1278
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Tidskriftsartikel (refereegranskat)abstract
- Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets was MET, a receptor tyrosine kinase activated by hepatocyte growth factor, that is crucial for metastatic progression.Results:We confirmed the inhibitory effect of miR-34c on both MET transcript and protein levels. The binding of miR-34c to two binding sites in the 3'-UTR of MET was validated using luciferase reporter assays and target site blockers. The effect of this regulation on the miR-34c inhibition of the migratory phenotype was also confirmed. In addition, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in PCa patients.Conclusion:These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.British Journal of Cancer advance online publication, 6 August 2013; doi:10.1038/bjc.2013.449 www.bjcancer.com.
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| 3. |
- Rohrmann, S., et al.
(författare)
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Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:3, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
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