Exp Mol Med.  2003 Oct;35(5):379-384.

Dexamethasone-induced differentiation of pancreatic AR42J cell involves p21(waf1/cip1)and MAP kinase pathway

• Eum WS
• Li MZ
• Sin GS
• Choi SY
• Park JB
• Lee JY
• Kwon HY

Abstract

Dexamethasone converts pluripotent pancreatic AR42J cells into exocrine cells expressing digestive enzymes. In order to address molecular mechanism of this differentiation, we have investigated the role of mitogen-activated protein (MAP) kinase pathway and gene expressions of p21(waf1/cip1)and nuclear oncogenes (c-fos and c-myc) during AR42J cell differentiation. Dexamethasone markedly increased the intracellular and secreted amylase contents as well as its mRNA level. However, cell growth and DNA content were significantly decreased. With these phenotypic changes, AR42J cells induced transient mRNA expression of p21(waf1/cip1)gene, which reached maximal level by 6 h and then declined gradually toward basal state. In contrast to p21(waf1/cip1), c-fos gene expression was transiently inhibited by 6 h and then recovered to basal level by 24 h. Increased c-myc expression detected after 3 h, peaked by 12 h, and remained elevated during the rest of observation. Dexamethasone inhibited epidermal growth factor-induced phosphorylation of extracellular signal regulated kinase. Inhibition of MAP kinase pathway by PD98059 resulted in further elevation of the dexamethasone-induced amylase mRNA and p21(waf1/cip1)gene expression. These results suggest that p21(waf1/cip1)and nuclear oncogenes are involved in dexamethasone-induced differentiation and inhibition of MAP kinase pathway accelerates the conversion of undifferentiated AR42J cells into amylase-secreting exocrine cells.

MeSH Terms

Amylases/genetics
Animals
Cell Differentiation/*drug effects
Cell Division/drug effects
Cell Line, Tumor
Cyclins/genetics/*metabolism
Dexamethasone/*pharmacology
Gene Expression Regulation/drug effects
Genes, fos/genetics
Genes, myc/genetics
MAP Kinase Signaling System/*drug effects
Mitogen-Activated Protein Kinases/*metabolism
Pancreas/cytology/*drug effects/enzymology/metabolism
RNA, Messenger/genetics/metabolism
Rats
Support, Non-U.S. Gov't