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Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism.

Publication ,  Journal Article
Shin, S; Asano, T; Yao, Y; Zhang, R; Claret, F-X; Korc, M; Sabapathy, K; Menter, DG; Abbruzzese, JL; Reddy, SAG
Published in: Mol Cancer Res
May 2009

Activator protein-1 (AP-1) regulates the expression of several genes involved in human tumorigenesis. However, there is little known about this transcription factor in pancreatic ductal adenocarcinoma. We recently found high levels of AP-1-binding activities and multiple AP-1/DNA complexes containing c-Jun, JunD, Fra1, and Fra2 in pancreatic cancer cells. Transient transfection assays indicated that AP-1 was functional and capable of transactivating its gene targets. Furthermore, a c-Jun transactivation mutant inhibited anchorage-dependent and anchorage-independent proliferation, suggesting that AP-1 had an essential role in pancreatic cancer cells. Our study also uncovered a novel mechanism by which protein kinase Akt controls c-Jun activity in pancreatic cancer cells. Indeed, distinct from its known ability to induce c-fos and fra1 and to stabilize c-Jun, Akt appeared to directly regulate the transcriptional activity of c-Jun independently of the phosphorylation sites targeted by c-Jun NH(2)-terminal kinase (Ser(63)/Ser(73)) and glycogen synthase kinase-3 (Thr(239)). Our data also suggest that growth factors might use this Akt-regulated mechanism to potently induce c-Jun targets such as cyclin D1. Collectively, our findings indicate that AP-1 has an important function in pancreatic cancer cells and provide evidence for a previously unknown Akt-mediated mechanism of c-Jun activation.

Duke Scholars

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

May 2009

Volume

7

Issue

5

Start / End Page

745 / 754

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factor AP-1
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-akt
  • Protein Binding
  • Phosphatidylinositol 3-Kinases
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
 

Citation

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MLA
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Shin, S., Asano, T., Yao, Y., Zhang, R., Claret, F.-X., Korc, M., … Reddy, S. A. G. (2009). Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism. Mol Cancer Res, 7(5), 745–754. https://doi.org/10.1158/1541-7786.MCR-08-0462
Shin, Sonyo, Takayuki Asano, Yixin Yao, Ronghua Zhang, Francois-Xavier Claret, Murray Korc, Kanaga Sabapathy, David G. Menter, James L. Abbruzzese, and Shrikanth A. G. Reddy. “Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism.Mol Cancer Res 7, no. 5 (May 2009): 745–54. https://doi.org/10.1158/1541-7786.MCR-08-0462.
Shin S, Asano T, Yao Y, Zhang R, Claret F-X, Korc M, et al. Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism. Mol Cancer Res. 2009 May;7(5):745–54.
Shin, Sonyo, et al. “Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism.Mol Cancer Res, vol. 7, no. 5, May 2009, pp. 745–54. Pubmed, doi:10.1158/1541-7786.MCR-08-0462.
Shin S, Asano T, Yao Y, Zhang R, Claret F-X, Korc M, Sabapathy K, Menter DG, Abbruzzese JL, Reddy SAG. Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism. Mol Cancer Res. 2009 May;7(5):745–754.

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

May 2009

Volume

7

Issue

5

Start / End Page

745 / 754

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factor AP-1
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-akt
  • Protein Binding
  • Phosphatidylinositol 3-Kinases
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis