Title

A Functional Nuclear Epidermal Growth Factor Receptor, Src and Stat3 Heteromeric Complex in Pancreatic Cancer Cells

Authors

Authors

S. Jaganathan; P. B. Yue; D. C. Paladino; J. Bogdanovic; Q. Huo;J. Turkson

Comments

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Abbreviated Journal Title

PLoS One

Keywords

DYNAMIC LIGHT-SCATTERING; GOLD NANOPARTICLE PROBES; NF-KAPPA-B; SIGNAL; TRANSDUCER; GENE-REGULATION; EGF RECEPTOR; CYTOPLASMIC TRANSPORT; ADENOCARCINOMA CELLS; TRANSCRIPTION FACTOR; DRUG DISCOVERY; Multidisciplinary Sciences

Abstract

Evidence is presented for the nuclear presence of a functional heteromeric complex of epidermal growth factor (EGFR), Src and the Signal Transducer and Activator of Transcription (Stat) 3 proteins in pancreatic cancer cells. Stat3 remains nuclear and associated with Src or EGFR, respectively, upon the siRNA knockdown of EGFR or Src, demonstrating the resistance of the complex to the modulation of EGFR or Src alone. Significantly, chromatin immunoprecipitation (ChIP) analyses reveal the nuclear EGFR, Src and Stat3 complex is bound to the c-Myc promoter. The siRNA knockdown of EGFR or Src, or the pharmacological inhibition of Stat3 activity only marginally suppressed c-Myc expression. By contrast, the concurrent modulation of Stat3 and EGFR, or Stat3 and Src, or EGFR and Src strongly suppressed c-Myc expression, demonstrating that the novel nuclear heteromeric complex intricately regulates the c-Myc gene. The prevalence of the transcriptionally functional EGFR, Src, and Stat3 nuclear complex provides an additional and novel mechanism for supporting the pancreatic cancer phenotype and explains in part the insensitivity of pancreatic cancer cells to the inhibition of EGFR, Src or Stat3 alone.

Journal Title

Plos One

Volume

6

Issue/Number

5

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

13

WOS Identifier

WOS:000290256400034

ISSN

1932-6203

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