PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin.
The pancreatic beta- and alpha-cells are developmentally related to each other but reveal diverse gene expression patterns. Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. To elucidate the function of PDX-1 in the expression of beta-cell-specific genes, we established stable alphaTC1 clone 6 (alphaTC1.6)-derived transfectants expressing PDX-1 and examined the changes in the gene expression patterns in them. The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression.
Watada
H
H
First Department of Medicine, Osaka University School of Medicine, Suita City, Japan.
Kajimoto
Y
Y
Miyagawa
J
J
Hanafusa
T
T
Hamaguchi
K
K
Matsuoka
T
T
Yamamoto
K
K
Matsuzawa
Y
Y
Kawamori
R
R
Yamasaki
Y
Y
D000682:Amyloid / Q000235:genetics; D066259:Betacellulin; D015870:Gene Expression / Q000187:drug effects*; D005941:Glucokinase / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology*; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000682:Amyloid; C587851:BTC protein, human; D066259:Betacellulin; D006133:Growth Substances; D018398:Homeodomain Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005941:Glucokinase