title: Intracellular ATP-binding cassette transporter A3 is expressed in lung cancer cells and modulates susceptibility to cisplatin and paclitaxel.
abstract: Patients with advanced-stage bronchial cancer benefit from systemic cytostatic therapy, in particular from regimens integrating cisplatin and taxanes. However, eventual disease progression leads to a fatal outcome in most cases, originating from tumor cells resisting chemotherapy. We here show that the intracellular ATP-binding cassette transporter A3 (ABCA3), previously recognized as critical for the secretion of surfactant components from type 2 pneumocytes, is expressed in non-small-cell lung cancer (NSCLC) cells. With some heterogeneity in a given specimen, expression levels detected immunohistochemically in primary cancer tissue were highest in adenocarcinomas and lowest in small cell lung cancers. Genetic silencing of ABCA3 in the NSCLC cell line models A549, NCI-H1650 and NCI-H1975 significantly increased tumor cell susceptibility to the cytostatic effects of both cisplatin (in all cell lines) and paclitaxel (in two of three cell lines). Taken together, ABCA3 emerges as a modulator of NSCLC cell susceptibility to cytostatic therapy.
authors.affiliation: Department of Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany. tobias.overbeck @ med.uni-goettingen.de
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Overbeck
authors.forename: Timo
authors.initials: T
authors.lastname: Hupfeld
authors.forename: Doris
authors.initials: D
authors.lastname: Krause
authors.forename: Regina
authors.initials: R
authors.lastname: Waldmann-Beushausen
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.forename: Bjoern
authors.initials: B
authors.lastname: Güldenzoph
authors.forename: Thiha
authors.initials: T
authors.lastname: Aung
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Schöndube
authors.forename: Bernhard C
authors.initials: BC
authors.lastname: Danner
authors.forename: Lorenz
authors.initials: L
authors.lastname: Truemper
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Wulf
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine