Kim Chul Jang, Yoshioka Naohisa, Tambe Yukihiro, Kushima Ryoji, Okada Yusaku, Inoue Hirokazu
Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Int J Cancer. 2005 Oct 20;117(1):51-8. doi: 10.1002/ijc.21120.
We have previously reported that expression of periostin mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that downregulation of periostin mRNA expression is correlated with the development of human cancers. In our study, to clarify the role of the periostin in human bladder carcinogenesis, we examined the expression of periostin mRNA in normal bladder tissues, bladder cancer tissues and bladder cancer cell lines by Northern blot analysis and RT-PCR analysis. Although the expression of periostin mRNA was detected in 100% (5/5) of normal bladder tissues, it was not detected in 3 human bladder cancer cell lines examined. It was also detected in 81.8% (9/11) of grade 1, 40.0% (4/10) of grade 2 and 33.3% (4/12) of grade 3 bladder cancer tissues, indicating that downregulation of periostin mRNA is significantly related to higher grade bladder cancer (p<0.05). To assess the tumor suppressor function of periostin, we investigated the ability of periostin gene to suppress malignant phenotypes of a bladder cancer cell line, SBT31A. Ectopic expression of periostin gene by a retrovirus vector suppressed in vitro cell invasiveness of the bladder cancer cells without affecting cell proliferation and tumor growth in nude mice. Periostin also suppressed in vivo lung metastasis of the mouse melanoma cell line, B16-F10. Mutational analysis revealed that the C-terminal region of periostin was sufficient to suppress cell invasiveness and metastasis of the cancer cells. Periostin may play a role as a suppressor of invasion and metastasis in the progression of human bladder cancers.
我们之前报道过，在多种人类癌细胞系中骨膜蛋白mRNA的表达显著降低，这表明骨膜蛋白mRNA表达的下调与人类癌症的发生发展相关。在我们的研究中，为了阐明骨膜蛋白在人类膀胱癌发生中的作用，我们通过Northern印迹分析和逆转录-聚合酶链反应（RT-PCR）分析检测了正常膀胱组织、膀胱癌组织及膀胱癌细胞系中骨膜蛋白mRNA的表达。虽然在100%（5/5）的正常膀胱组织中检测到了骨膜蛋白mRNA的表达，但在所检测的3个人类膀胱癌细胞系中未检测到。在1级膀胱癌组织的81.8%（9/11）、2级的40.0%（4/10）和3级的33.3%（4/12）中也检测到了该蛋白，这表明骨膜蛋白mRNA的下调与高级别膀胱癌显著相关（p<0.05）。为了评估骨膜蛋白的肿瘤抑制功能，我们研究了骨膜蛋白基因抑制膀胱癌细胞系SBT31A恶性表型的能力。通过逆转录病毒载体异位表达骨膜蛋白基因可抑制膀胱癌细胞的体外侵袭能力，而不影响细胞增殖及裸鼠体内肿瘤生长。骨膜蛋白还可抑制小鼠黑色素瘤细胞系B16-F10的体内肺转移。突变分析显示，骨膜蛋白的C末端区域足以抑制癌细胞的侵袭和转移。骨膜蛋白可能在人类膀胱癌进展过程中作为侵袭和转移的抑制因子发挥作用。
