Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype
Joint Authors
To, Kenneth K. W.
Cheng, Grace M. Y.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-14
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
ABCG2 is an efflux transporter commonly found to overexpress in multidrug resistant (MDR) cancer cells.
It is also believed to be a survival factor for cancer stem cells to drive tumor growth.
Tumor microenvironment represents an attractive new drug target because it allows complex interaction between a tumor and its surrounding normal cells, molecules, and blood vessels, which all participate in tumor progression.
Hypoxia, glucose deprivation and acidosis are the hallmarks of tumor microenvironment.
This study investigated the upregulation of ABCG2 by these adverse growth conditions within the tumor microenvironment.
Reporter gene assay revealed that a region within the ABCG2 promoter close to the reported HIF-1α response element is responsible for ABCG2 upregulation.
Increased ABCG2 efflux activity was observed under the same conditions, subsequently leading to reduced response to ABCG2 substrate anticancer drug.
Importantly, glucose deprivation and hypoxia were also found to enhance the resistance level of ABCG2-overexpressing resistant cells with pre-existing genetic and epigenetic MDR mechanisms.
Hypoxia was further demonstrated to cause a more malignant anchorage-independent growth phenotype in the resistant cells, which can be abolished by knocking down ABCG2.
A better understanding of ABCG2 regulation by the tumor microenvironment may help design novel strategies to improve treatment outcome.
American Psychological Association (APA)
Cheng, Grace M. Y.& To, Kenneth K. W.. 2012. Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype. ISRN Oncology،Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-495373
Modern Language Association (MLA)
Cheng, Grace M. Y.& To, Kenneth K. W.. Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype. ISRN Oncology No. 2012 (2012), pp.1-10.
https://search.emarefa.net/detail/BIM-495373
American Medical Association (AMA)
Cheng, Grace M. Y.& To, Kenneth K. W.. Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype. ISRN Oncology. 2012. Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-495373
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-495373