Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080 China.
J Exp Clin Cancer Res. 2010 Dec 11;29(1):161. doi: 10.1186/1756-9966-29-161.
Pim-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.
Expression 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.
When 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.
Our 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.
Pim-1 是一种丝氨酸/苏氨酸激酶,可在肿瘤发生过程中促进早期转化、细胞增殖和细胞存活。多项研究表明,Pim-1 激酶在不同类型的癌症中发挥作用,然而,Pim-1 在膀胱癌中的作用知之甚少。
通过免疫组织化学检测人正常和恶性膀胱标本中 Pim-1 的表达和定位,并比较 Pim-1 染色评分与几种临床病理参数。为了进一步证明 Pim-1 在膀胱癌中的生物学功能,通过 Western blot 和免疫组织化学分析验证了其在五种膀胱癌细胞系中的表达。随后通过慢病毒编码小干扰 RNA 实现 Pim-1 的敲低,并通过集落形成和细胞增殖测定进一步评估 Pim-1 对膀胱细胞存活和药物敏感性的影响。
与正常上皮相比,Pim-1 在膀胱癌上皮中过度表达,且在浸润性膀胱癌标本中表达水平高于非浸润性膀胱癌标本。在本研究中检测的所有膀胱癌细胞系中均检测到 Pim-1。此外,Pim-1 的敲低显著抑制了膀胱癌细胞的生长,并在体外使细胞对化疗药物敏感。
本研究结果表明,Pim-1 可能在膀胱癌的发生和发展中起作用。由于 Pim-1 还参与了膀胱癌细胞的存活和耐药性,因此 Pim-1 是膀胱癌靶向治疗的潜在候选药物。