Kim Chul Jang, Isono Takahiro, Tambe Yukihiro, Chano Tokuhiro, Okabe Hidetoshi, Okada Yusaku, Inoue Hirokazu
Department of Urology, Kohka Public Hospital, Kohka, Shiga 528-0014, Japan.
Int J Oncol. 2008 Jan;32(1):161-9.
We have previously reported that the expression of periostin mRNA is significantly repressed in human bladder cancer tissues, and that periostin plays a role as a suppressive factor for invasion and metastasis in the progression of human bladder cancers. In this study, to clarify the role of alternative splicing of periostin in human bladder carcinogenesis, we examined the expression of wild-type (WT) and spliced variants of periostin mRNA in normal bladder and bladder cancer tissues. Although both WT and spliced periostin mRNA were expressed in all normal bladder tissues examined, no WT periostin mRNA was detected in the examined transitional cell carcinomas (TCCs) of the bladder (0/23) or in bladder cancer cell lines (0/6). Spliced variants of periostin were detected in 48% (11/23) of TCC tissues and 33% (2/6) of bladder cancer cell lines. Two types of spliced periostin (Variants I and II) were successfully isolated from bladder cancer tissues, but Variant I, which is predominantly expressed in bladder cancer tissues, did not show suppressor activity on in vitro invasiveness and in vivo metastasis of cancer cells. Immunohistochemical analysis indicated that strong belt-like expression of periostin protein was observed in the stroma just beneath the normal bladder epithelium, while it was mostly attenuated in bladder cancer tissues. These results indicate that the loss of WT periostin by down-regulation and/or alternative splicing, which produces Variant I, is closely correlated with the development of bladder cancer.
我们之前曾报道，骨膜蛋白mRNA在人膀胱癌组织中的表达显著受到抑制，并且骨膜蛋白在人膀胱癌进展过程中作为侵袭和转移的抑制因子发挥作用。在本研究中，为了阐明骨膜蛋白可变剪接在人膀胱癌发生中的作用，我们检测了正常膀胱组织和膀胱癌组织中骨膜蛋白mRNA野生型（WT）和剪接变体的表达。虽然WT和剪接的骨膜蛋白mRNA在所有检测的正常膀胱组织中均有表达，但在所检测的膀胱移行细胞癌（TCC）（0/23）或膀胱癌细胞系（0/6）中未检测到WT骨膜蛋白mRNA。在48%（11/23）的TCC组织和33%（2/6）的膀胱癌细胞系中检测到骨膜蛋白的剪接变体。从膀胱癌组织中成功分离出两种类型的剪接骨膜蛋白（变体I和变体II），但主要在膀胱癌组织中表达的变体I对癌细胞的体外侵袭性和体内转移没有显示出抑制活性。免疫组织化学分析表明在正常膀胱上皮下方的基质中观察到骨膜蛋白呈强带状表达，而在膀胱癌组织中大多减弱。这些结果表明WT骨膜蛋白通过下调和/或产生变体I的可变剪接而缺失与膀胱癌的发生密切相关。
