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

Publication ,  Journal Article
Asano, T; Yao, Y; Zhu, J; Li, D; Abbruzzese, JL; Reddy, SA
Published in: Biochem Biophys Res Commun
May 27, 2005

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.

Duke Scholars

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

May 27, 2005

Volume

331

Issue

1

Start / End Page

295 / 302

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Proto-Oncogene Proteins c-jun
  • Protein Kinases
  • Phosphorylation
  • Pancreatic Neoplasms
  • Mutation
  • Immunohistochemistry
  • Humans
 

Citation

APA
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ICMJE
MLA
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Asano, T., Yao, Y., Zhu, J., Li, D., Abbruzzese, J. L., & Reddy, S. A. (2005). The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation. Biochem Biophys Res Commun, 331(1), 295–302. https://doi.org/10.1016/j.bbrc.2005.03.166
Asano, Takayuki, Yixin Yao, Jijiang Zhu, Donghui Li, James L. Abbruzzese, and Shrikanth A. Reddy. “The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation.Biochem Biophys Res Commun 331, no. 1 (May 27, 2005): 295–302. https://doi.org/10.1016/j.bbrc.2005.03.166.
Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SA. The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation. Biochem Biophys Res Commun. 2005 May 27;331(1):295–302.
Asano, Takayuki, et al. “The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation.Biochem Biophys Res Commun, vol. 331, no. 1, May 2005, pp. 295–302. Pubmed, doi:10.1016/j.bbrc.2005.03.166.
Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SA. The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation. Biochem Biophys Res Commun. 2005 May 27;331(1):295–302.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

ISSN

0006-291X

Publication Date

May 27, 2005

Volume

331

Issue

1

Start / End Page

295 / 302

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Proto-Oncogene Proteins c-jun
  • Protein Kinases
  • Phosphorylation
  • Pancreatic Neoplasms
  • Mutation
  • Immunohistochemistry
  • Humans