Regulation of Gastrin Gene Expression by Phorbol Ester in AGS Cells

• Main Authors: Hui-Ting Chang, 張惠婷
• Other Authors: Wen-Chang Chang
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/35980759250910106716

碩士 === 國立成功大學 === 藥理學研究所 === 91 === The peptide hormone gastrin, expressed in the gastrointestinal tract and pancreas, is an important regulator of gastric acid secretion and growth factor of the gastrointestinal mucosa. The expression of gastrin was under tightly developmental and tissue specific control. It was reported that EGF activated the transcription of gastrin in human gastric adenocarcinoma AGS cells through Ras-ERK signaling pathway. Besides, the Sp1 binding site residing at —68 to —61 bp of gastrin promoter plays an important role in the EGF-induced gene expression. Previously, our laboratory had reported that EGF and PMA enhanced the biosynthesis of c-Jun in A431 cells, which subsequently induced the transcription of 12(S)-lipoxygenase by interacting with Sp1. We also found that treatment of the AGS cells with PMA enhanced the expression of c-Jun. Therefore, we want to identify the regulation mechanisms of PMA-induced expression of gastrin and to analyze the role of c-Jun/Sp1 interaction in the regulation of gastrin gene expression in AGS cells. In this report, we found that PMA, an activator of PKC, induced the gene expression of gastrin in a time-dependent manner in AGS cells. Transient transfection with a series of 5’-deletion mutants revealed that the 5’-flanking region spanning from -82 to -40 bp and —40 to +66 bp were important for the PMA-induced gastrin gene activation in AGS cells. From the result of gel shift assay, it indicated that Sp1 will bind with the DNA oligonucleotide probe spanning the promoter region —71/-51 and —52/-31. However, the Sp1 sites residing at -68 to -61 bp and -44 to -40 bp of gastrin promoter were not involved in PMA-induced expression of gastrin gene, but involved in basal expression. Except that, TATA box and the downstream element (-28 to +66 bp) also play an important role in PMA-induced gastrin activation in AGS cells.