title: Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells.
abstract: Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, Malaysia. Electronic address: aisya735@puncakalam.uitm.edu.my.
authors.forename: Aisyah H
authors.initials: AH
authors.lastname: Jahidin
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: teneale.stewart@uq.edu.au.
authors.forename: Teneale A
authors.initials: TA
authors.lastname: Stewart
authors.affiliation: Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, Australia; Queensland University of Technology Translational Research Institute, Brisbane, Queensland, Australia. Electronic address: e2.thompson@qut.edu.au.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Thompson
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: sarahrt@uq.edu.au.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Roberts-Thomson
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; Mater Research, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia; The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. Electronic address: gregm@uq.edu.au.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Monteith
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D015640:Ion Channel Gating; D014746:Vimentin / Q000378:metabolism*; D000097903:Two-Pore Channels
chemical_list: D002118:Calcium; D015220:Calcium Channels; D066246:ErbB Receptors; D014746:Vimentin; C407357:TPCN1 protein, human; D000097903:Two-Pore Channels; C530224:TPCN2 protein, human; C512478:EGFR protein, human
keywords: Breast cancer; Calcium; Calcium signaling; Epidermal growth factor; Two-pore channel; Vimentin