title: Phorbol 12,13 dibutyrate behaves in a tumor-inhibitory manner in esophageal adenocarcinoma cell lines.
abstract: Esophageal cancer is an extremely lethal human disease. Relatively little is known about the molecular mechanisms leading to esophageal cancers, nor the signaling pathways activated to maintain and augment the tumor growth. Esophageal cancer cell lines were evaluated to assess the effect of phorbol 12,13 dibutyrate on protein kinase C activity, indirectly using protein kinase D (formerly known as protein kinase C-μ), Akt activity, and cell proliferation. Treatment of esophageal cancer cell lines with the phorbol ester phorbol 12,13 dibutyrate led to a rapid and dramatic increase in the activation of protein kinase D. In addition, administration of phorbol 12,13 dibutyrate also decreased the phosphorylation of Akt. Interestingly, in the OE19 esophageal adenocarcinoma cell line, treatment with phorbol 12,13 dibutyrate also led to inhibition of cell growth. All the phorbol ester effects observed were reversible by combined treatment with a protein kinase C inhibitor, implicating protein kinase C in the cells' response to the phorbol ester. Overall, these studies suggest that protein kinase D (e.g. protein kinase C-μ) may behave as a tumor suppressor in some esophageal cancer samples, serving to inhibit Akt activity and block cell growth.
authors: Department of Thoracic Surgery, University of California-Los Angeles, CA, USA. mmaish@mednet.ucla.edu
authors: M S
authors: MS
authors: Maish
authors: M
authors: M
authors: Carballo
authors: A
authors: A
authors: Yetasook