The Human ABCG2 (ATP Binding Cassette Subfamily G Member 2) gene, also known as BCRP (Breast Cancer Resistance Protein), encodes a member of the ATP-binding cassette (ABC) transporter family. ABCG2 is involved in the efflux of various compounds, including drugs, toxins, and xenobiotics, from cells. This transport activity plays a significant role in drug resistance, particularly in cancer cells, and can affect the pharmacokinetics and efficacy of certain medications.
The MDCKII (Madin-Darby Canine Kidney) cell line, which is derived from canine kidney epithelial cells, has been engineered to stably express the Human ABCG2 gene. This stable cell line is a valuable resource for studying the function of ABCG2 in drug transport and resistance. Researchers can use the MDCKII ABCG2 stable cell line to investigate the transport mechanisms of ABCG2, its role in cellular drug resistance, and its interaction with other cellular components. This cell line also provides a platform for the development of strategies to overcome ABCG2-mediated drug resistance, which is crucial for the effective treatment of cancer and other diseases.
In bovine mammary glands, the ABCG2 transporter plays an active role in pumping xenobiotics into dairy milk. The researchers investigated the effects of 13 commonly used pesticides in Europe on AhR activation and bABCG2 efflux activity using MDCKII cells expressing mammary bABCG2. Pesticides were applied at concentrations equivalent to maximum residue levels (MRLs) in bovine fat or muscle. Prochloraz, a known AhR activator, served as a positive control, and tolclofos-methyl as a negative control. Chlorpyrifos-methyl, diflufenican, ioxynil, rimsulfuron, and tebuconazole significantly increased CYP1A1 mRNA levels, CYP1A activity, and bABCG2 efflux compared to controls. Conversely, dimethoate, dimethomorph, glyphosate, iprodione, methiocarb, and thiacloprid showed no AhR activation or bABCG2 induction. MDCKII-bABCG2 cells proved effective in identifying AhR- and bABCG2-inducing pesticides, offering an in vitro alternative to animal-based studies for pesticide risk assessment.
Figure 1. The researchers assessed MDCKII-bABCG2 cells' response to AhR-activating pesticides. After 24-hour exposure at 10-fold MRL concentrations, Hoechst 33342 accumulation was measured with or without the ABCG2-inhibitor Ko143 (5 μM). (Kuhnert L, et al., 2020)
Human ABCG2 Stable Cell Line - MDCKII, due to its overexpression of the ABCG2 protein, is an essential tool in the study of pharmacological and physiological processes. The ABCG2 gene encodes a member of the ATP-binding cassette (ABC) transporters, which are involved in ATP-driven transport of many substances across cellular membranes.
(1) Cancer Drug Resistance Research
The ABCG2 protein is known to contribute to the development of resistance to cancer chemotherapy by actively effluxing a wide range of anticancer drugs from malignant cells. Utilizing the Human ABCG2 Stable Cell Line - MDCKII, researchers can investigate the mechanisms of drug resistance in cancer cells, screen for new drugs that can overcome resistance, and develop strategies to modulate ABCG2 activity to enhance the efficacy of chemotherapy.
(2) Toxicology and Safety Pharmacology
In the realm of toxicology, Human ABCG2 Stable Cell Line - MDCKII can be employed to study the role of ABCG2 in the protection against xenobiotic toxicity. This cell line is instrumental in evaluating the potential toxicity of new chemical entities (NCEs) and their ability to be effluxed by ABCG2, thereby affecting their safety profile.
(3) Nutrient Absorption and Metabolic Studies
ABCG2 also plays a role in the absorption and disposition of various dietary compounds. The Human ABCG2 Stable Cell Line - MDCKII can be used to study the transport of nutritional components, such as vitamins and minerals, and their bioavailability. Additionally, it helps in understanding the role of ABCG2 in the metabolism and excretion of these compounds, which has implications for nutritional science and diet-based therapies.
Customer Q&As
How was the Human ABCG2 Stable Cell Line - MDCKII established, and what is its origin?
A: The Human ABCG2 Stable Cell Line - MDCKII was established by transfecting the human ABCG2 gene into MDCKII (Madin-Darby Canine Kidney II) cells. MDCKII cells are a canine kidney cell line commonly used in vitro studies. The human ABCG2 gene encodes a multidrug resistance protein, and its transfection into MDCKII cells allows for the expression of the ABCG2 protein, thus creating this stable cell line.
How does the expression level of the ABCG2 gene in the Human ABCG2 Stable Cell Line - MDCKII compare to the original MDCKII cells?
A: The expression level of the ABCG2 gene in the Human ABCG2 Stable Cell Line - MDCKII is significantly higher than in the original MDCKII cells. By transfecting the human ABCG2 gene, the cells acquire additional copies of the ABCG2 gene, resulting in increased expression levels of this gene and consequently higher production of the multidrug resistance protein.
What are the characteristics of multidrug resistance in the Human ABCG2 Stable Cell Line - MDCKII?
A: The Human ABCG2 Stable Cell Line - MDCKII exhibits pronounced multidrug resistance characteristics, primarily due to its high-level expression of the ABCG2 protein. ABCG2 is an ATP-binding cassette transporter protein that forms channels on the cell membrane, facilitating the efflux of various drugs from the cell and conferring multidrug resistance.
How is the Human ABCG2 Stable Cell Line - MDCKII used in screening potential drug resistance reversal agents?
A: The Human ABCG2 Stable Cell Line - MDCKII can be employed in high-throughput screening of potential drug resistance reversal agents. By exposing these cells to candidate compounds and observing changes in their sensitivity to drugs, promising compounds capable of reversing multidrug resistance can be identified.
What are the structural features of the ABCG2 protein in the Human ABCG2 Stable Cell Line - MDCKII?
A: The ABCG2 protein in the Human ABCG2 Stable Cell Line - MDCKII possesses a transmembrane structure, forming channels on the cell membrane. Its structural features include two nucleotide-binding domains and multiple transmembrane regions, collectively constituting the functional domain of the ABCG2 protein.
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Drug Efflux Research
The Human ABCG2 Stable Cell Line - MDCKII is an ideal model for studying the drug efflux mechanism mediated by ABCG2.
Drug Sensitivity Assessment
This cell line can be used to evaluate the sensitivity of drugs to ABCG2-mediated multidrug resistance.
Drug Interaction Analysis
Contributes to the analysis of drug interactions with the ABCG2 protein and their impact on drug efficacy.
United Kingdom
05/25/2022
Biomembrane Research
Utilizes the MDCKII cell line to study the function of ABCG2 in biomembrane formation and maintenance.
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