Related Experiment Video
Updated: Jul 8, 2026

A Convenient and General Expression Platform for the Production of Secreted Proteins from Human Cells
Published on: July 31, 2012
P-glycoprotein: so many ways to turn it on
Richard Callaghan1, Emily Crowley, Simon Potter
1Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. richard.callaghan@ndcls.ox.ac.uk
Abstract:
Expression of the ABC transporter P-glycoprotein (P-gp or ABCB1) is associated with resistance to chemotherapy in cancer. However, early investigations into the regulation of ABCB1 expression revealed that the process is not a classical induction as observed for certain metabolizing enzymes. The process involves the cellular stress response pathway initiated by either inflicted (e.g., chemotherapy damage) or endogenous (e.g., hypoxia) factors. However, ABCB1 is also expressed in a number of noncancerous tissues. In particular, the protein is found at tissues providing a barrier or secretory function. The localization of ABCB1 in normal tissues will impact significantly on drug pharmacokinetics, in particular the absorption and elimination processes. This review also describes the mechanism underlying ABCB1 expression in noncancerous tissue, a process that does not involve the stress response.
Insights
P-glycoprotein (P-gp or ABCB1) expression drives chemotherapy resistance via cellular stress. However, ABCB1 in normal tissues functions differently, impacting drug pharmacokinetics without stress response involvement.
Area of Science:
- Biochemistry
- Pharmacology
- Cancer Biology
Background:
- P-glycoprotein (P-gp or ABCB1) is an ABC transporter linked to chemotherapy resistance in cancer.
- ABCB1 expression is regulated by cellular stress pathways, triggered by chemotherapy or hypoxia.
- ABCB1 is also present in noncancerous tissues, particularly at barrier and secretory sites.
Purpose of the Study:
- To review the regulation of ABCB1 expression in both cancerous and noncancerous tissues.
- To elucidate the distinct mechanisms of ABCB1 expression in normal tissues.
- To understand the impact of ABCB1 localization on drug pharmacokinetics.
Main Methods:
- Literature review of studies on ABCB1 expression and regulation.
- Analysis of ABCB1 localization in normal physiological barriers.
- Comparison of ABCB1 regulation in cancer versus noncancerous tissues.
Main Results:
- ABCB1 expression in cancer is often linked to cellular stress responses.
- ABCB1 is found in barrier tissues (e.g., blood-brain barrier, gut epithelium) and secretory organs.
- ABCB1 expression in noncancerous tissues does not appear to involve the classical stress response pathway.
Conclusions:
- ABCB1 plays a critical role in drug pharmacokinetics, affecting absorption and elimination due to its presence in normal tissues.
- Understanding the distinct regulatory mechanisms of ABCB1 in normal tissues is crucial for drug development and treatment strategies.
- The differential regulation of ABCB1 highlights its complex role beyond chemotherapy resistance.
Related Concept Videos
GPCRs Regulate Adenylyl Cylase Activity
Two...
Amplifying Signals via Enzymatic Cascade
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical, 7TM, or...
cAMP-dependent Protein Kinase Pathways
Activation and Inactivation of G Proteins
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...

