Background: Members of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined.
Methods: The expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting.
Results: Higher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6.
Conclusion: Our results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.
Keywords: CCT3; TRiC; chaperonin containing TCP-1; gastric cancer.