title: TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells.
abstract: Highly Ca(2+) permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium, the activity of nuclear factor of activated T-cells (NFAT) and proliferation of BON-1 cells. TRPV6 expression was assessed by real-time PCR and Western blot. TRPV6 mRNA expression and protein production were down-regulated by siRNA. Changes in intracellular calcium levels were detected by fluorescence calcium imaging (fura-2/AM). NFAT activity was studied by NFAT reporter assay; cell proliferation by bromodeoxyuridine (BrdU), MTT and propidium iodine staining. TRPV6 mRNA and protein are present in BON-1 and QGP-1 NET-cells. Down-regulation of TRPV6 attenuates BON-1 cell proliferation. TRPV6 down-regulation is associated with decreased Ca(2+) response pattern and reduced NFAT activity. In conclusion, TRPV6 is expressed in pancreatic NETs and modulates cell proliferation via Ca(2+)-dependent mechanism, which is accompanied by NFAT activation.
authors.affiliation: Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, 60-637 Poznań, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Skrzypski
authors.affiliation: Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, 60-637 Poznań, Poland Department of Hepatology and Gastroenterology and Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, 13353 Berlin, Germany.
authors.forename: Paweł A
authors.initials: PA
authors.lastname: Kołodziejski
authors.affiliation: Department of Ophthalmology, Charité-University Medicine Berlin, 13353 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mergler
authors.affiliation: Institute for Experimental Pediatric Endocrinology, Charité-University Medicine Berlin, 13353 Berlin, Germany.
authors.forename: Noushafarin
authors.initials: N
authors.lastname: Khajavi
authors.affiliation: Department of Animal Physiology and Biochemistry, Poznań University of Life Sciences, 60-637 Poznań, Poland.
authors.forename: Krzysztof W
authors.initials: KW
authors.lastname: Nowak
authors.affiliation: Department of Hepatology and Gastroenterology and Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, 13353 Berlin, Germany Medical Clinic 1, Department of Gastroenterology, Elblandklinik, 01662 Meissen, Germany mathias.strowski@charite.de.
authors.forename: Mathias Z
authors.initials: MZ
authors.lastname: Strowski
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D002118:Calcium
keywords: BON-1; QGP-1; TRPV6; calcium; neuroendocrine tumour; proliferation