title: Overexpression of wild-type PKD2 leads to increased proliferation and invasion of BON endocrine cells.
abstract: Carcinoid tumors are rare neuroendocrine tumors with a predilection for the gastrointestinal tract. Protein kinase D (PKD), a novel serine/threonine protein kinase, has been implicated in the regulation of transport processes in certain cell types. We have reported an important role for PKD in stimulated peptide secretion from a human (BON) carcinoid cell line; however, the role of PKD isoforms, including PKD2, in the proliferation and invasion of carcinoid tumors remains unclear. In the present study, we found that overexpression of PKD2 by stable transfection of BON cells with PKD2-wild type (PKD2WT) significantly increased proliferation and invasion compared to cells transfected with PKD2-kinase dead (PKD2KD) or pcDNA3 (control). Similarly, inhibition of PKD2 activity with small interfering RNA (siRNA) significantly decreased proliferation and invasion compared to cells transfected with non-targeting control (NTC) siRNA. These data support an important role for PKD2 in carcinoid tumor progression. Targeted inhibition of the PKD family may prove to be a novel treatment option for patients with carcinoid tumors.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Jackson
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: L Andy
authors.initials: LA
authors.lastname: Chen
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
mesh_terms: D002276:Carcinoid Tumor / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D014162:Transfection
chemical_list: D000091283:Protein Kinase D2; D011494:Protein Kinases