title: Leukotriene B4 induces EMT and vimentin expression in PANC-1 pancreatic cancer cells: Involvement of BLT2 via ERK2 activation.
abstract: Leukotriene B4(LTB4) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB4is known to be correlated with cancer progression. LTB4induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB4in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB4induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR. LTB4induced morphological change, decreased E-cadherin expression and increased N-cadherin and vimentin expression. LTB4 increased migration and invasion of PANC-1 cancer cells. LTB4dose-dependently upregulated expression of vimentin in PANC-1 cancer cells. LTB4-induced vimentin expression was suppressed by LY255283 (BLT2 antagonist). Comp A, a BLT2 agonist, further increased vimentin expression. Gene silencing of BLT2 suppressed LTB4-or Comp A-induced vimentin expression in PANC-1 cells. The MEK inhibitor, PD98059 suppressed Comp A-induced vimentin expression. Comp A or transfection of plasmid containing BLT2 cDNA (pCBLT2) activated ERK, and BLT2 gene silencing suppressed Comp A-induced ERK activation. ERK2 siRNA abrogated Comp A-induced vimentin expression and ERK2 overexpression enhanced vimentin expression. One of well-known cause of ras mutation, cigarette smoke extracts increased BLT2 expression in PANC-1 cancer cells. Taken together, these results suggest that BLT2 is involved in LTB4-induced vimentin expression through ERK2 in PANC-1 cells.
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: You Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Gyeong Jin
authors.initials: GJ
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Moo-Yeol
authors.initials: MY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: uatheone@dongguk.edu.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
chemical_list: C485878:LTB4R2 protein, human; D018102:Receptors, Leukotriene B4; D014746:Vimentin; D007975:Leukotriene B4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
keywords: BLT2; Comp A; EMT; ERK2; LTB(4); Vimentin