{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:34:06Z","timestamp":1791074046985,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T00:00:00Z","timestamp":1198108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death. Smoking, diabetes, and pancreatitis are risk factors. It has been shown that the growth of PDAC and pancreatic duct epithelial cells is regulated by beta\u2010adrenoreceptors (\u03b2\u2010ARs). The activity of \u03b2\u2010ARs in the central nervous system is counteracted by \u03b3\u2010aminobutyric acid (GABA) via GABA<jats:sub>B<\/jats:sub> receptor\u2010mediated inhibition of adenylyl cyclase. The aim of the study was to investigate if GABA<jats:sub>B<\/jats:sub>R inhibits \u03b2\u2010AR signaling in PDAC and pancreatic duct epithelial cells, thus blocking driving forces of cancer progression, such as cell proliferation and cell migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>Intracellular cAMP was measured by immunoassays, DNA synthesis by BrdU incorporation assays, activation of ERK1\/2 by ERK activation assays, and Western blots and metastatic potential by cell migration assays in the human PDAC cell lines PANC\u20101 and BXPC\u20103 and immortalized human pancreatic duct epithelial cells HPDE6\u2010C7. The expression of norepinephrine, PKAR<jats:sub>II\u03b1<\/jats:sub>, and GABA in PDAC microarrays was assessed by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Stimulation of the GABA<jats:sub>B<\/jats:sub>R by GABA or baclofen inhibited isoproterenol\u2010induced cAMP signaling below base levels. ERK1\/2 activity in response to isoproterenol was blocked by GABA, an effect enhanced by transient overexpression of the GABA<jats:sub>B<\/jats:sub>R and abolished by GABA<jats:sub>B<\/jats:sub>R knockdown. DNA synthesis and cell migration were stimulated by isoproterenol, responses blocked by GABA and baclofen. Norepinephrine and PKAR<jats:sub>II\u03b1<\/jats:sub> were overexpressed while GABA was underexpressed in human PDAC tissue arrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>The data suggest the stimulation of GABA<jats:sub>B<\/jats:sub>R signaling as a novel target for the treatment and prevention of pancreatic cancer. Cancer 2008. \u00a9 2007 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.23231","type":"journal-article","created":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T15:19:47Z","timestamp":1198163987000},"page":"767-778","source":"Crossref","is-referenced-by-count":96,"title":["GABA<sub>B<\/sub> receptor is a novel drug target for pancreatic cancer"],"prefix":"10.1002","volume":"112","author":[{"given":"Hildegard M.","family":"Schuller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein A. 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