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PMID: 9769331 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro.

The Journal of clinical investigation ·Vol. 102 ·No. 7 ·1998-10-01 ·Pages 1385-92

Grandis JR, Drenning SD, Chakraborty A, Zhou MY, Zeng Q, Pitt AS, Tweardy DJ

Abstract

Stimulation of epidermal growth factor receptor (EGFR) by ligand(s) leads to activation of signaling molecules including Stat1 and Stat3, two members of the signal transducers and activators of transcription (STAT) protein family. Activation of Stat1 and Stat3 was constitutive in transformed squamous epithelial cells, which produce elevated levels of TGF-alpha, and was enhanced by the addition of exogenous TGF-alpha. Targeting of Stat3 using antisense oligonucleotides directed against the translation initiation site, resulted in significant growth inhibition. In addition, cells stably transfected with dominant negative mutant Stat3 constructs failed to proliferate in vitro. In contrast, targeting of Stat1 using either antisense or dominant-negative strategies had no effect on cell growth. Thus, TGF-alpha/EGFR-mediated autocrine growth of transformed epithelial cells is dependent on activation of Stat3 but not Stat1.

MeSH Terms
Carcinoma, Hepatocellular Carcinoma, Squamous Cell Cell Division/drug effects Cells, Cultured DNA-Binding Proteins/metabolism Epithelial Cells/cytology,drug effects,physiology ErbB Receptors/drug effects,physiology Head and Neck Neoplasms Humans Kinetics Liver Neoplasms Mouth Mucosa/cytology,drug effects,physiology Recombinant Proteins/pharmacology STAT1 Transcription Factor STAT3 Transcription Factor Trans-Activators/metabolism Transforming Growth Factor alpha/pharmacology,physiology Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Recombinant Proteins STAT1 Transcription Factor STAT1 protein, human STAT3 Transcription Factor STAT3 protein, human Trans-Activators Transforming Growth Factor alpha ErbB Receptors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Grandis J R
Department of Otolaryngology, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. [email protected]
Drenning S D
Chakraborty A
Zhou M Y
Zeng Q
Pitt A S
Tweardy D J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI3785
Email
[email protected]
Published
1998-10-01
Pages
1385-92
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508986
Subset
IM
Grants
NCI NIH HHS · CA 72261 · United States
NCI NIH HHS · CA01760 · United States
NCI NIH HHS · CA72526 · United States
External Links
PubMed source DOI: 10.1172/JCI3785 PMC Full Text View journal details
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