Secretion of MUC5AC mucin from pancreatic cancer cells in response to forskolin and VIP.
MUC5AC mucin is not expressed in normal pancreas but is expressed in tumors. Little is known about the mechanisms that lead to this atypical expression. In this study, we demonstrate that stimulation of adenylyl cyclase and the protein kinase A (PKA) pathway by forskolin and vasoactive intestinal peptide (VIP) increased MUC5AC antigen expression and release from pancreatic cancer cells. Stimulation of the PKA pathway also increased MUC5AC mRNA. When SW1990 pancreatic cancer cells were grown on porous membranes they released MUC5AC mucins apically in response to VIP (10(-7) M) applied to their basolateral surfaces. SW1990 cells, as have been reported for other pancreatic cancer cells, have high affinity (<10(-7) M) VIP receptors and low affinity (>10(-6) M) secretin receptors. We also showed that four antibodies (CLH2, 21M1, 45M1, and Nd2) react with MUC5AC antigen in different cellular compartments of both tissues and cultured cells. In conclusion, the PKA pathway may contribute to the up-regulation of MUC5AC expression seen in pancreatic tumors.
Ho
Jenny J L
JJ
Gastrointestinal Research Laboratory (151 M2), Veterans Medical Center and Department of Medicine, University of California, San Francisco, CA 94121, USA. jjl@itsa.ucsf.edu
Crawley
Suzanne
S
Pan
Pamela L
PL
Farrelly
Ellyn R
ER
Kim
Young S
YS
D005576:Colforsin / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005765:Gastrointestinal Agents; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D011493:Protein Kinase C