Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells.
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.
Tachibana
I
I
Gastroenterology Research Unit, Saint Marys Hospital, Mayo Clinic, Rochester, Minnesota 55905, USA.
Imoto
M
M
Adjei
P N
PN
Gores
G J
GJ
Subramaniam
M
M
Spelsberg
T C
TC
Urrutia
R
R
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D051765:Early Growth Response Transcription Factors; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D015723:Gene Library; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010190:Pancreatic Neoplasms; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; C491385:Klf10 protein, rat; D051741:Kruppel-Like Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta