Shiotani A, Merchant J L
Howard Hughes Medical Institute Research Laboratories, University of Michigan Medical Center, Ann Arbor 48109-0650, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):G458-64. doi: 10.1152/ajpgi.1995.269.3.G458.
Gastrin is one of the most potent regulators of acid secretion and gastrointestinal cell growth. A variety of signals regulate gastrin release from the antral G cell. However, whether these secretagogues also stimulate gastrin gene expression has not been established. Dramatic increases in gastrin gene expression occur in the stomach after birth and in response to chronic achlorhydria. Moreover, gastrin gene expression in malignant islet cell tumors (gastrinomas) appears to represent reactivation of the fetal pattern of expression in the pancreas. Thus differential expression of the gastrin gene is a reflection of differences in transcriptional control. Since various luminal and humoral factors stimulate the production of cAMP and gastrin secretion in both gastrinoma and antral G cells, we studied the effect of cAMP on gastrin gene expression. Using stable and transient transformants of a pituitary cell line containing the human gastrin gene, we found that cAMP stimulates a three-fold increase in gastrin mRNA levels and that the response maps to elements located between -148 and -40 base pairs upstream from the cap site. Collectively, these studies link an important regulator of gastrin secretion to regulation of gastrin gene expression.
胃泌素是胃酸分泌和胃肠道细胞生长最有效的调节因子之一。多种信号调节胃窦G细胞释放胃泌素。然而，这些促分泌素是否也刺激胃泌素基因表达尚未确定。出生后以及对慢性胃酸缺乏作出反应时，胃中胃泌素基因表达会急剧增加。此外，恶性胰岛细胞瘤（胃泌素瘤）中的胃泌素基因表达似乎代表了胰腺中胎儿期表达模式的重新激活。因此，胃泌素基因的差异表达反映了转录控制的差异。由于各种腔内和体液因素刺激胃泌素瘤和胃窦G细胞中cAMP的产生和胃泌素分泌，我们研究了cAMP对胃泌素基因表达的影响。利用含有人类胃泌素基因的垂体细胞系的稳定和瞬时转化体，我们发现cAMP刺激胃泌素mRNA水平增加三倍，并且该反应定位于帽位点上游-148至-40碱基对之间的元件。总的来说，这些研究将胃泌素分泌的一个重要调节因子与胃泌素基因表达的调节联系起来。
