The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation.

Published

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

Pubmed Central 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