title: The expressions of ABCC4 and ABCG2 xenobiotic transporters in human keratinocytes are proliferation-related.
abstract: Xenobiotic transporters of the ATP-binding cassette (ABC) protein superfamily play important roles in maintaining the biochemical barrier of various tissues, but their precise functions in the skin are not yet known. Screening of the expressions of the known xenobiotic transporter genes in two in vitro keratinocyte differentiation models revealed that the ABCC4 and ABCG2 transporters are highly expressed in proliferating keratinocytes, their expressions decreasing along with differentiation. Abrogation of the ABCC4 and ABCG2 protein functions by siRNA-mediated silencing and chemical inhibition did not affect the proliferation of HaCaT cells. In contrast, disruption of the ABCG2 function had no effect on normal human epidermal keratinocyte proliferation, while the inhibition of ABCC-type transporters by probenecid resulted in a striking decrease in the proliferation of the cells. These results indicate that, besides their possible therapy-modulating effects, xenobiotic transporters may contribute significantly to other keratinocyte functions, such as cell proliferation.
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Hungary. bebes.attila@gmail.com
authors.forename: Attila
authors.initials: A
authors.lastname: Bebes
authors.forename: Kornélia
authors.initials: K
authors.lastname: Kis
authors.forename: Tünde
authors.initials: T
authors.lastname: Nagy
authors.forename: Anita
authors.initials: A
authors.lastname: Kurunczi
authors.forename: Hilda
authors.initials: H
authors.lastname: Polyánka
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bata-Csörgo
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemény
authors.forename: Attila
authors.initials: A
authors.lastname: Dobozy
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D053556:Keratin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D039081:Integrin alpha5beta1; D053556:Keratin-1; D019394:Ki-67 Antigen; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011339:Probenecid; D034741:RNA, Small Interfering; D015262:Xenobiotics; C073492:ABCC4 protein, human; C116614:ABCG2 protein, human