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摘要
Although PLC epsilon has been verified to enhance bladder cancer cell invasion, the signaling pathways responsible for this remain elusive. Protein kinase C (PKC alpha/beta), which is involved in cancer development and progression, has been demonstrated to be activated by PLC epsilon. However, the roles of PKC alpha/beta in PLC epsilon-mediated bladder carcinoma cell invasion and migration have not been clearly identified. In this study, to determine what role PKC alpha/beta plays in PLC epsilon-mediated bladder cancer cell invasion and migration, we silenced PLC epsilon gene by adenovirus-shPLC epsilon in T24 and BIU-87 cells and then revealed that it significantly inhibited cell migration and invasion. Further research indicated that cell bio-function of PLC epsilon-regulated was related with PKC alpha/beta activity. These in vitro findings were supported by data from bladder carcinoma patient samples. In 35 case bladder cancer tumor samples, PLC epsilon-overexpressing tumors showed significantly higher positive rates of PKC alpha/beta membrane immunohistochemistry staining than PLC epsilon-low-expressing tumors. Mechanistically, study further showed that PLC epsilon knockdown gene induced E-cadherin expression and decreased TBX3 expression, both of which were dependent on PKC alpha/beta activity. In addition, we demonstrated that treatment cells with TBX3-specific shorting hairpin RNA (shRNA) up-regulated E-cadherin expression and inhibited cell invasion/migration. Moreover, in in vivo experiment, immunohistochemistry analysis of Ad-shPLC epsilon-infected tumor tissue showed low expression levels of phospho-PKC alpha/beta and TBX3 and high expression levels of E-cadherin compared with those of the control group. In summary, our findings uncover that PKC alpha/beta is critical for PLC epsilon-mediated cancer cell invasion and migration and provide valuable insights for current and future Ad-shPLC epsilon and PKC alpha/beta clinical trials.
- 出版日期2014-3
- 单位重庆医科大学
