The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation.
Journal Article (Journal Article)
We present immunohistochemical evidence that the mTOR/p70s6k pathway is activated in pancreatic tumors and show that the mTOR inhibitor and rapamycin analog CCI-779 potently suppresses the proliferation of pancreatic cancer cells. Consistent with a recent study, CCI-779 increased c-Jun phosphorylation (Ser63) in a dose- and time-dependent manner, and induced apoptosis in p53-defective BxPC-3 cells. In contrast to the study, however, we observed that CCI-779 concomitantly increased c-Jun protein levels and that its ability to induce apoptosis might not require the activated c-Jun. Furthermore, CCI-779 neither induced c-Jun phosphorylation in other p53-defective pancreatic cancer cells (MiaPaCa-2) nor inhibited their proliferation. c-Jun, in fact, appeared to be partly responsible for the resistance of MiaPaCa-2 cells to CCI-779. Together, these results indicate a complex role for c-Jun in cellular responses to CCI-779 and provide an important basis for investigating CCI-779 further as a potential therapeutic agent for pancreatic tumors.
Full Text
Duke Authors
Cited Authors
- Asano, T; Yao, Y; Zhu, J; Li, D; Abbruzzese, JL; Reddy, SA
Published Date
- May 27, 2005
Published In
Volume / Issue
- 331 / 1
Start / End Page
- 295 - 302
PubMed ID
- 15845392
International Standard Serial Number (ISSN)
- 0006-291X
Digital Object Identifier (DOI)
- 10.1016/j.bbrc.2005.03.166
Language
- eng
Conference Location
- United States