|CSC-DC000069||Panoply™ Human ABCG2 Knockdown Stable Cell Line||Inquiry|
|CSC-SC000069||Panoply™ Human ABCG2 Over-expressing Stable Cell Line||Inquiry|
|CDCB156622||Cynomolgus ABCG2 ORF clone||Inquiry|
|CDCR023062||Human ABCG2 ORF clone (NM_004827.2)||Inquiry|
|CDCR023068||Mouse Abcg2 ORF clone (NM_011920.3)||Inquiry|
|CDCR382009||Rat Abcg2 ORF Clone(NM_181381.2)||Inquiry|
|CDFH000075||Human ABCG2 cDNA Clone(NM_004827.2)||Inquiry|
|CDFH000076||Human ABCG2 cDNA Clone(NM_004827.2)||Inquiry|
|CDFR014962||Rat Abcg2 cDNA Clone(NM_181381.2)||Inquiry|
|MiUTR1H-00059||ABCG2 miRNA 3'UTR clone||Inquiry|
|MiUTR1M-01057||ABCG2 miRNA 3'UTR clone||Inquiry|
|MiUTR1R-00037||ABCG2 miRNA 3'UTR clone||Inquiry|
|SHG025237||shRNA set against Human ABCG2(NM_004827.2)||Inquiry|
|SHG025255||shRNA set against Mouse Abcg2(NM_011920.3)||Inquiry|
|SHG025309||shRNA set against Rat Abcg2(NM_181381.2)||Inquiry|
|SHH229306||shRNA set against Human ABCG2 (NM_004827.2)||Inquiry|
|SHH229310||shRNA set against Mouse ABCG2 (NM_011920.3)||Inquiry|
|SHH229314||shRNA set against Rat ABCG2 (NM_181381.2)||Inquiry|
ATP-binding cassette superfamily G member 2 (ABCG2) is a member of the ATP-binding cassette (ABC) transporter superfamily and is a P-glycoprotein (P-glycoprotein, P-gp). This protein was discovered by Doyle et al. in the breast cancer cell line MCF-7/Adrvp3000 and is therefore referred to as a breast cancer resistance protein; it is then found to be abundantly expressed on the placenta. It was therefore identified as a new member of the ABC transporter superfamily. ABCG2 consists of 655 amino acids and contains only one transmembrane domain and one ATP-binding domain, hence the term "half-molecule ABC transporter." The ABCG2 transporter is associated with blood uric acid levels and the prevalence of gout. ABCG2 dysfunction reduces uric acid excretion, which can cause gout. Stiburkova et al. found that non-synonymous allelic variants of ABCG2 have a significant impact on the presence of early gout attacks and familial gout history.
ABCG2 is mainly expressed in human placental tissue and is also distributed in the brain, prostate, small intestine, testis, ovary, and liver. Most of the current research focuses on gene expression and transcription of ABCG2. The ABCG2 promoter region has two cis-elements, an estrogen response element, and a hypoxia response element, and a peroxisome proliferator activated receptor g (PPARg) response element located upstream of the ABCG2 gene. PPARg controls the expression of the ABCG2 gene. The study found that progesterone up-regulates the expression of ABCG2 by estrogen response elements on the promoter, and certain cytokines also affect the function of ABCG2 by regulating ABCG2 gene expression.
ABCG2 Protein Major Biological Function
In recent years, research on ABCG2 transporter-related functions has been increasing. The study found that as a transmembrane drug pump, the high expression of ABCG2 can promote the transport of endogenous substances and various anti-tumor drugs. The efflux effect of the ABCG2 transmembrane drug pump can limit the intake of drugs from the blood circulation to the brain, placenta, and testis, as well as the clearance of drugs in intestinal epithelial cells, hepatocytes and renal tubular cells.
Uric acid is the final product of sputum metabolism in the human body. The kidney plays an important role in uric acid excretion. Two-thirds of the uric acid in the body is mainly excreted by the kidney. However, the mechanism of renal excretion of uric acid is very complex, including glomerular filtration, tubular reabsorption, and secretion. Studies have shown that multiple transporters and ion channels on the apical and basement membranes of renal tubular epithelial cells are associated with reabsorption and secretion of uric acid. The uric acid transporter urate anion transporter 1, fructose transporter 9 is expressed in the apical and basement membranes of proximal tubular epithelial cells. The organic anion transporters 1, 2 and 3 are expressed in the basolateral membrane. As well as ABCG2, phosphate transporter 1 and 4, multidrug resistance protein 4 and other involved in the reabsorption and secretion of uric acid, play an important role in the regulation of blood uric acid concentration, is an important target for the treatment of hyperuricemia.
Figure 1. The dysfunction of urate exporter ABCG2 is revealed to cause RUE hyperuricemia as well as ROL hyperuricemia due to blockade of urate excretion from the kidney and intestine, respectively. (Matsuo, et al. 2014).
Studies have calculated cumulative radioactive uric acid clearance on Xenopus laevis oocytes expressing the human ABCG2 protein, and found that intracellular urate levels are significantly decreased, confirming that ABCG2 protein expressed on oocytes can promote uric acid excretion. The researchers used a potassium oxonate as a modeling agent to establish a mouse model of hyperuricemia. Since the ABCG2 transporter is an ATP-dependent protein, the expression of ABCG2 protein was significantly up-regulated in mice after adding ATP to the model group, and uric acid excretion was significantly increased compared with the mice not in the ATP group. Compared with normal control mice, the ABCG2 knockout group showed a significant increase in blood uric acid levels and a significant increase in urinary creatinine. Another ABCG2 knockout experiment also confirmed that the intestinal uric acid clearance rate in the knockout group was significantly lower than that in the normal group, which further confirmed that ABCG2 dysfunction can cause elevated blood uric acid levels.
ABCG2 and Cancer
Since the discovery of ABCG2 and tumor resistance, many scholars have devoted themselves to the study of the expression and function of ABCG2 in various malignant tumors, thus finding a new way to treat tumors. Wang et al. performed immunohistochemical staining on 120 patients with clear cell renal cell carcinoma to analyze the expression of ABCG2. Overall survival was analyzed using the Kaplan-Meier method and multivariate Cox regression was used to assess independent predictors of overall survival. It was found that ABCG2 can be used as a prognostic marker for the overall survival of patients with clear cell renal cell carcinoma. Sasaki et al. studied the effect of ABCG2 on the malignant characteristics of stem cells (CSC) in pancreatic ductal adenocarcinoma (PDAC). In this study, the investigators compared the characteristics of low (ABCG2-) and high (ABCG2+)-ABCG2-expressing PDAC cells after cell sorting. ABCG2-cells were found to produce ABCG2+ cells, and the malignant potential of ABCG2+ cells in PDAC varied depending on the environment in which they were placed. Sun et al. selected 9 potential functional single nucleotide polymorphisms from three genes in the clinical cohort of 1001 non-small cell lung cancer (NSCLC) patients in China and genotyped them. We found that the variant genotype of ABCG2 rs3114020 was associated with a significant increase in the risk of death from NSCLC, suggesting that ABCG2 rs3114020 may be one of the candidate biomarkers for NSCLC survival in the Chinese population.
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