Faculty Collaboration Database

Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J Clin Invest 1997 May 15;99(10):2365-74

Date

05/15/1997

Pubmed ID

9153278

Pubmed Central ID

PMC508075

DOI

10.1172/JCI119418

Scopus ID

2-s2.0-0030610532 (requires institutional sign-in at Scopus site)   196 Citations

Abstract

Members of the TGFbeta family of peptides exert antiproliferative effects and induce apoptosis in epithelial cell populations. In the exocrine pancreas, these peptides not only regulate normal cell growth, but alterations in these pathways have been associated with neoplastic transformation. Therefore, the identification of molecules that regulate exocrine pancreatic cell proliferation and apoptotic cell death in response to TGFbeta peptides is necessary for a better understanding of normal morphogenesis as well as carcinogenesis of the pancreas. In this study, we have characterized the expression and function in exocrine pancreatic epithelial cells of the TGFbeta-inducible early gene (TIEG), a Krüppel-like zinc finger transcription factor encoding gene previously isolated from mesodermally derived osteoblastic cells. We demonstrate that this gene is expressed in both acinar and ductular epithelial cell populations from the exocrine pancreas. In addition, we show that the expression of TIEG is regulated by TGFbeta1 as an early response gene in pancreatic epithelial cell lines. Moreover, overexpression of TIEG in the TGFbeta-sensitive epithelial cell line PANC1 is sufficient to induce apoptosis. Together, these results support a role for TIEG in linking TGFbeta-mediated signaling cascades to the regulation of pancreatic epithelial cell growth.

Author List

Tachibana I, Imoto M, Adjei PN, Gores GJ, Subramaniam M, Spelsberg TC, Urrutia R

Author

Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Amino Acid Sequence
Animals
Apoptosis
Cell Division
Cell Line
Consensus Sequence
DNA-Binding Proteins
Early Growth Response Transcription Factors
Epithelial Cells
Epithelium
Gene Expression
Gene Library
Humans
Kruppel-Like Transcription Factors
Male
Molecular Sequence Data
Organ Specificity
Pancreas
Pancreatic Neoplasms
Rats
Recombinant Fusion Proteins
Sequence Homology, Amino Acid
Transcription Factors
Transfection
Transforming Growth Factor beta
Tumor Cells, Cultured
Zinc Fingers