Abstract
BackgroundPim-1 is a serine-threonine kinase which promotes early transformation, cell proliferation and cell survival during tumorigenesis. Several studies have demonstrated that Pim-1 kinase play a role in different cancer types, however, the function of Pim-1 in bladder cancer is poorly understood.MethodsExpression and localization of Pim-1 in human normal and malignant bladder specimens were examined by Immunohistochemistry and Pim-1 staining score was compared with several clinicopathologic parameters. To further demonstrate the biological function of Pim-1 in bladder cancer, its expression was validated in five bladder cancer cell lines by western blot and immunohistochemistry analyses. Subsequent knockdown of Pim-1 was achieved by lentivirus encoding small interfering RNA, and the effect of Pim-1 on bladder cell survival and drug sensitivity were further assessed by colony formation and cell proliferation assays.ResultsWhen compared with normal epithelium, Pim-1 was overexpressed in bladder cancer epithelium, and the expression level was higher in invasive bladder cancer than Non-invasive bladder cancer specimens. Pim-1 was also detected in all the bladder cancer cell lines examined in our study. Moreover, the knockdown of Pim-1 significantly inhibited bladder cancer cell growth and also sensitized cells to chemotherapeutic drugs in vitro.ConclusionsOur results in this study suggest that Pim-1 may play a role in bladder cancer initiation and progression. Since Pim-1 is also involved in bladder cancer cell survival and drug resistance, Pim-1 is a potential candidate for targeted therapy in bladder cancer.
Highlights
Pim-1 is a serine-threonine kinase which promotes early transformation, cell proliferation and cell survival during tumorigenesis
Overexpression of Pim-1 in human bladder cancer specimens To validate the expression of Pim-1 protein in bladder cancer, human bladder specimens containing normal epithelium (n = 21) and malignant tissues (n = 45) were studied by immunohistochemistry using Pim-1 antibody
The staining data showed that Pim-1 expression is weakely detect in the epithelial cells of normal bladder epithelium, most of the malignant bladder epithelial cells exhibited Pim-1 immunoreactivity in both cytoplasm and nuclear (Figure 1)
Summary
Pim-1 is a serine-threonine kinase which promotes early transformation, cell proliferation and cell survival during tumorigenesis. An average of 10% to 20% for Non-invasive tumors may further progress to muscle-invasive disease, lead to eventual radical Cystectomy and urinary diversion [1,2,3]. In this context, clinicians face challenges to identify the novel therapeutic targets for bladder cancer. As a member of serine/threonine kinase family, Pim-1 has multiple roles in tumorigenesis such as promoting transformation and cell proliferation partly through regulation of cell cycle and transcription by phosphorylating of number of substrates including cdc25A/C, HP1, and p100 [9,10,11]. The aims of the present study are to investigate the expression level of Pim-1 in bladder cancer tissue and study its function in the pathogenesis and progression of bladder cancer
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