Breast, lung, prostate, gastric, colorectal, head and neck, pancreas, nasopharyngeal carcinoma, neuroblastoma and glioblastoma, glioma, leukemia Chemistry and retinoblastoma. It has been shown that cancer cells with ABCG2 expression SP more of a lasting ex vivo expansion, asymmetric division, h Here tumorigenesis in vivo was. Some studies have GSK1904529A reported that cancer cells with or without ABCG2 expression and tumorigenic and therefore raises the question of whether ABCG2 does not R The stemness of cancer cells. Further studies are absolutely necessary for the expression and R Aufzukl of ABCG2 in the putative cancer stem cells Ren.
Substrates of ABCG2 substrates ABCG2 directly cellular by testing Rer or vesikul Identified major transport, or indirectly through the substrate-stimulated ATPase activity of Agomelatine t or cytotoxicity Tstests, cover a wide range of cancer drugs, glucuronide and sulfate conjugates of sterols and of xenobiotics, toxins and natural compounds, fluorescent dyes, photosensitizers and antibiotics. One of the key components of ABCG2 substrates of drugs against cancer confinement Lich topoisomerase inhibitors, anthracyclines, camptothecin analogs, tyrosine kinase inhibitors, and antimetabolites. ABCG2 also transports sulfate and glucuronide many stero And of xenobiotics, the two common products of phase II metabolism in S Ugetieren are suggesting that that ABCG2 is important in the metabolic pathways of drugs. ABCG2 also mediates the efflux of pheophorbide a, chlorophyll, and many other photosensitizers, with ABCG2 as an m Possible reasons for the resistance of photodynamic therapy.
Interestingly, ABCG2 may also be in the transport of peptides A on the blood-brain barrier and the regulation of ABCG2 is correlated with a statement in cerebrovessels, which will be used at angiopathy Amylo Of the brain in Alzheimer’s disease patients with. Interestingly, in early studies with MCF-7 / AdVp3000 or mitoxantrone selected Hlt S1 lines M1 cells, 80, was the transport of rhodamine 123 was observed. However, the bertragungskapazit t not of rhodamine 123 seen in other cell lines overexpressing ABCG2. This inconsistency has led to the discovery of a mutant ABCG2 R482G gain of function with / T mutation R482G and R482T ABCG2 in two mutants and wild-type capable of efflux of mitoxantrone, topotecan, SN 38, Hoechst 33342 and BODIPY prazosin.
However the mutants R482G and R482T a gr Affinity ere t for anthracyclines, including doxorubicin, daunorubicin, epirubicin, and fluorescent dye rhodamine 123 bisantrene and LysoTracker green. Only the wild-type ABCG2 can tats Chlich take methotrexate, MTX and diglutamate triglutamate and folic Acid. These data suggest that the amino Acid 482 can a place, and elegant setting, transmission, and this mutation affects the substrate specificity be T of ABCG2. However, a study IAARh123 showed the photoreactive analogue of rhodamine 123, surprisingly, that the wild-type ABCG2 with the R482T mutants R482G both k can All bind directly to IAARh123 although the wild-type ABCG2 could not carry rhodamine. This observation indicates not only the direct binding of substrates for ABCG2, but also on the Unf Ability of wild-type ABCG2 transport rhodamine 123 can not be anf Held nglichen level of binding. In Foll