Overexpression of the TGF beta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells
Overexpression of the TGF beta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells
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DOI：
10.1172/jci119418
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发表时间：
1997-05-15
影响因子：
15.9
通讯作者：
Urrutia, R
中科院分区：
文献类型：
--
作者：
Tachibana, I;Imoto, M;Urrutia, R
TGF β肽家族的成员在上皮细胞群中发挥抗增殖作用并诱导凋亡。在胰腺外分泌中，这些肽不仅调节正常细胞生长，而且这些途径的改变与肿瘤转化有关。因此，识别调节外分泌胰腺细胞增殖和凋亡细胞死亡的分子，以响应TGF β肽是必要的，以更好地了解正常形态发生以及胰腺癌的发生。在这项研究中，我们的特点是表达和功能的外分泌胰腺上皮细胞的TGF β诱导早期基因（TIEG），Kruppel样锌指转录因子编码基因以前分离的中胚层来源的成骨细胞。我们证明，该基因表达在胰腺外分泌腺泡和导管上皮细胞群。此外，我们发现TIEG的表达受TGF β 1作为胰腺上皮细胞系中的早期反应基因的调节。此外，TIEG在TGF β敏感性上皮细胞系PANC 1中的过表达足以诱导细胞凋亡。总之，这些结果支持TIEG在将TGF β介导的信号级联与胰腺上皮细胞生长的调节联系起来中的作用。
Members of the TGF beta 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 TGF beta 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 TGF beta-inducible early gene (TIEG), a Kruppel-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 TGF beta 1 as an early response gene in pancreatic epithelial cell lines. Moreover, overexpression of TIEG in the TGF beta-sensitive epithelial cell line PANC1 is sufficient to induce apoptosis. Together, these results support a role for TIEG in linking TGF beta-mediated signaling cascades to the regulation of pancreatic epithelial cell growth.