Transient transcriptional activation of gastrin during sodium butyrate-induced differentiation of islet cells.
Transient expression of pancreatic gastrin corresponds to a period of rapid islet cell development. After birth gastrin expression silencing is coincidental with islet cell terminal differentiation, while persistent expression is accompanied with nesidioblastosis and reexpression observed in islet cell tumors. Experiments with transgenic animals suggested that gastrin might act synergistically with growth factors to stimulate islet cell development. The present study intended to establish an in vitro cell culture model to analyse the molecular events controlling gastrin gene activation and repression dependent on islet cell differentiation. Sodium butyrate, a proliferation-arresting compound has previously been shown to differentiate insulinoma cells while increasing insulin production. The present paper demonstrates concomitant transient increase in gastrin mRNA, intracellular and secreted gastrin during sodium butyrate treatment. Increased gastrin expression was due to activation or derepression of gastrin promoter activity as revealed by promoter analyses. This in vitro model mimics the expression pattern of gastrin and insulin observed during fetal islet cell development and provides an excellent tool to analyse the molecular mechanisms controlling gastrin gene activation and selective repression during islet cell differentiation.
Simon
B
B
Department of Internal Medicine, Philipps-University, Marburg, Germany. simonb@mailer.uni-marburg.de
Merchant
J L
JL
Eissele
R
R
Köhler
K
K
Arnold
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D005755:Gastrins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002087:Butyrates; D005755:Gastrins; D020148:Butyric Acid