Jody T Mack1, Carol B Brown, Kenneth D Tew. 1. Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, 173 Ashley Avenue, BSB 303, MSC 505, Charleston, South Carolina 29425-5050, USA.
Abstract
BACKGROUND: Overexpression of ATP-binding cassette (ABC) transporters is a major adaptive advantage used by tumor cells to evade the accumulation of cytotoxic agents. ABCA2, a transporter highly expressed in the cells of the nervous and haematopoetic systems, is associated with lipid transport and drug resistance in cancer cells, including tumor stem cells. Recently, a single nucleotide polymorphism (SNP) in Abca2 was linked to early onset Alzheimer's disease (AD). The characterization of two independent knockout mouse models has shed light on putative in vivo functions of this transporter in the development and maintenance of myelin membrane lipids in the CNS. OBJECTIVE: The objective of this review is to guide the reader through the existing scope of literature on the ABCA2 transporter, focusing on its potential as a future target in human pathologies, specifically cancer and neurological disease. METHODS: An NCBI PubMed literature search was conducted to address the growing body of ABCA2 literature that, at the time of publication, included 39 reports. From these, we focused on papers that provided insight into the functional importance of this transporter in tumor stem cells, cancer, drug resistance, Alzheimer's disease and myelination. RESULTS/ CONCLUSION: These studies have implicated ABCA2 as a therapeutic target in modulating the drug resistance phenotype prevalent in human cancers and in the treatment of neuropathies, including Alzheimer's disease and myelin-related disorders.
BACKGROUND: Overexpression of ATP-binding cassette (ABC) transporters is a major adaptive advantage used by tumor cells to evade the accumulation of cytotoxic agents. ABCA2, a transporter highly expressed in the cells of the nervous and haematopoetic systems, is associated with lipid transport and drug resistance in cancer cells, including tumor stem cells. Recently, a single nucleotide polymorphism (SNP) in Abca2 was linked to early onset Alzheimer's disease (AD). The characterization of two independent knockout mouse models has shed light on putative in vivo functions of this transporter in the development and maintenance of myelin membrane lipids in the CNS. OBJECTIVE: The objective of this review is to guide the reader through the existing scope of literature on the ABCA2 transporter, focusing on its potential as a future target in human pathologies, specifically cancer and neurological disease. METHODS: An NCBI PubMed literature search was conducted to address the growing body of ABCA2 literature that, at the time of publication, included 39 reports. From these, we focused on papers that provided insight into the functional importance of this transporter in tumor stem cells, cancer, drug resistance, Alzheimer's disease and myelination. RESULTS/ CONCLUSION: These studies have implicated ABCA2 as a therapeutic target in modulating the drug resistance phenotype prevalent in humancancers and in the treatment of neuropathies, including Alzheimer's disease and myelin-related disorders.
Authors: Jody T Mack; Kristi L Helke; Gabrielle Normand; CoDanielle Green; Danyelle M Townsend; Kenneth D Tew Journal: Cancer Lett Date: 2010-10-30 Impact factor: 8.679
Authors: Vasiliki Michaki; Francesc X Guix; Krist'l Vennekens; Sebastian Munck; Colin Dingwall; John B Davis; Danyelle M Townsend; Kenneth D Tew; Fabian Feiguin; Bart De Strooper; Carlos G Dotti; Tina Wahle Journal: J Biol Chem Date: 2011-11-15 Impact factor: 5.157
Authors: Ellen L Hedditch; Bo Gao; Amanda J Russell; Yi Lu; Catherine Emmanuel; Jonathan Beesley; Sharon E Johnatty; Xiaoqing Chen; Paul Harnett; Joshy George; Rebekka T Williams; Claudia Flemming; Diether Lambrechts; Evelyn Despierre; Sandrina Lambrechts; Ignace Vergote; Beth Karlan; Jenny Lester; Sandra Orsulic; Christine Walsh; Peter Fasching; Matthias W Beckmann; Arif B Ekici; Alexander Hein; Keitaro Matsuo; Satoyo Hosono; Toru Nakanishi; Yasushi Yatabe; Tanja Pejovic; Yukie Bean; Florian Heitz; Philipp Harter; Andreas du Bois; Ira Schwaab; Estrid Hogdall; Susan K Kjaer; Allan Jensen; Claus Hogdall; Lene Lundvall; Svend Aage Engelholm; Bob Brown; James Flanagan; Michelle D Metcalf; Nadeem Siddiqui; Thomas Sellers; Brooke Fridley; Julie Cunningham; Joellen Schildkraut; Ed Iversen; Rachel P Weber; Andrew Berchuck; Ellen Goode; David D Bowtell; Georgia Chenevix-Trench; Anna deFazio; Murray D Norris; Stuart MacGregor; Michelle Haber; Michelle J Henderson Journal: J Natl Cancer Inst Date: 2014-06-23 Impact factor: 13.506
Authors: Jerzy Trojan; Yuexin X Pan; Ming X Wei; Adama Ly; Alexander Shevelev; Maciej Bierwagen; Marie-Yvonne Ardourel; Ladislas A Trojan; Alvaro Alvarez; Christian Andres; Maria C Noguera; Ignacio Briceno; Beatriz H Aristizabal; Heliodor Kasprzak; Huynh T Duc; Donald D Anthony Journal: Chemother Res Pract Date: 2012-02-14