title: Bcl-2-dependent modulation of swelling-activated Cl- current and ClC-3 expression in human prostate cancer epithelial cells.
abstract: Cell shrinkage is an integral part of apoptosis. However, intimate mechanisms linking apoptotic events to the alterations in cell volume homeostasis remain poorly elucidated. We investigated how overexpression of Bcl-2 oncoprotein, a key antiapoptotic regulator, in lymph node carcinoma of the prostate (LNCaP) prostate cancer epithelial cells interferes with the volume-regulated anion channel (VRAC), a major determinant of regulatory volume decrease. Bcl-2 overexpression resulted in the doubling of VRAC-carried swelling-activated Cl(-) current (I(Cl,swell)) and weakened I(Cl,swell) inhibition by store-operated Ca(2+) channel (SOC)-transported Ca(2+). This also was accompanied by substantial up-regulation of ClC-3 protein, a putative molecular candidate for the role of VRAC. ClC-3-specific antibody suppressed I(Cl,swell) in the wild-type and Bcl-2-overexpressing LNCaP cells. Epidermal growth factor treatment of wild-type LNCaP cells, promoting their proliferation, resulted in the enhancement of endogenous Bcl-2 expression and associated increases in ClC-3 levels and I(Cl,swell) magnitude. We conclude that Bcl-2-induced up-regulation of I(Cl,swell), caused by enhanced expression of ClC-3 and weaker negative control from SOC-transported Ca(2+), would strengthen the ability of the cells to handle proliferative volume increases and thereby promote their survival and diminish their proapoptotic potential.
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bâtiment SN3, 59655 Villeneuve d'Ascq, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Lemonnier
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shuba
authors.forename: Alexandre
authors.initials: A
authors.lastname: Crepin
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mauroy
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D045744:Cell Line, Tumor; D048429:Cell Size / Q000502:physiology; D018118:Chloride Channels / Q000096:biosynthesis* / Q000235:genetics; D002712:Chlorides / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D004815:Epidermal Growth Factor