1. PIAS1 is not suitable as a urothelial carcinoma biomarker protein and pharmacological target
- Author
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Erb, Holger Hans Hermann, Ebert, Marlies, Kuhn, Ronja, Donix, Lukas, Haferkamp, Axel, Seed, Robert Ian, and Jüngel, Eva
- Subjects
Cell Viability Testing ,Urologic Neoplasms ,Science ,Cancer Treatment ,DNA repair ,Antineoplastic Agents ,Research and Analysis Methods ,Transfection ,Biochemistry ,Genetics ,Gene Expression and Vector Techniques ,Medicine and Health Sciences ,Tumor Cells, Cultured ,Humans ,Small interfering RNAs ,Non-coding RNA ,Molecular Biology Techniques ,Molecular Biology ,Cell Analysis ,Tumor Stem Cell Assay ,Cell Proliferation ,Molecular Biology Assays and Analysis Techniques ,Biology and life sciences ,Proteins ,DNA ,Prognosis ,Protein Inhibitors of Activated STAT ,SUMOylation ,Gene regulation ,Nucleic acids ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Bioassays and Physiological Analysis ,Oncology ,Small Ubiquitin-Related Modifier Proteins ,Medicine ,RNA ,Hyperexpression Techniques ,DNA damage ,Gene expression ,Post-translational modification ,Cisplatin ,Neoplasm Recurrence, Local ,Research Article - Abstract
Urothelial cancer (UC) is one of the most common cancers in Europe and is also one of the costliest to treat. When first line therapies show initial success, around 50% of cancers relapse and proceed to metastasis. In this study we assessed the Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1 as a potential therapeutic target in urothelial cancer. PIAS1 is a key regulator of STAT1 signalling and may be implicated in carcinogenesis. In contrast to other cancer types PIAS1 protein expression is not significantly different in malignant areas of UC specimens compared to non-malignant tissue. In addition, we found that down-regulation and overexpression of PIAS1 had no effect on the viability or colony forming ability of tested cell lines. Whilst other studies of PIAS1 suggest an important biological role in cancer, this study shows that PIAS1 has no influence on reducing the cytotoxic effects of Cisplatin or cell recovery after DNA damage induced by irradiation. Taken together, these in vitro data demonstrate that PIAS1 is not a promising therapeutic target in UC cancer as previously shown in different entities such as prostate cancer (PCa).
- Published
- 2019