Adenosine triphosphate-binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate-binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate-binding cassette gene expression profiles (signatures), based on the expression of all 49 human adenosine triphosphate-binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate-binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate-binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients-breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real-time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate-binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate-binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 (official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers. Graphical abstract.

• Klíčová slova
• Adenosine triphosphate–binding cassette, adenosine triphosphate–binding cassette transporters, bioinformatics, cancer, gene expression, profile,
• MeSH
• ABC transportéry biosyntéza   genetika   MeSH
• karcinogeneze * MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé MeSH
• nádory prsu genetika   patologie   MeSH
• nádory slinivky břišní genetika   patologie   MeSH
• protein CFTR biosyntéza   genetika   MeSH
• receptory sulfonylurey biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• transkriptom genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportéry MeSH
• ABCA12 protein, human MeSH Prohlížeč
• ABCA3 protein, human MeSH Prohlížeč
• ABCA8 protein, human MeSH Prohlížeč
• ABCC8 protein, human MeSH Prohlížeč
• CFTR protein, human MeSH Prohlížeč
• protein CFTR MeSH
• receptory sulfonylurey MeSH

Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity. In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHaCDV and HeLaCDV) and one HPV(-) (HaCaTCDV) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug-resistance (MRP2, P-gp, BCRP) was also investigated. Alterations of CDV metabolism in SiHaCDV and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHaCDV and HeLaCDV, respectively. Altered transporters expression in SiHaCDV and/or HeLaCDV, but not in HaCaTCDV, was also noted. Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process.

• Klíčová slova
• NTP metabolism, UMP-CMP kinase, cervical carcinoma, cidofovir, human papillomavirus,
• MeSH
• ABC transportéry biosyntéza   MeSH
• chemorezistence genetika   MeSH
• cidofovir MeSH
• cytidintrifosfát biosyntéza   MeSH
• cytosin analogy a deriváty   farmakologie   MeSH
• fosforylace MeSH
• HeLa buňky MeSH
• infekce papilomavirem farmakoterapie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• nádorové buněčné linie MeSH
• nádory děložního čípku farmakoterapie   patologie   virologie   MeSH
• nukleosidmonofosfátkinasa biosyntéza   metabolismus   MeSH
• organofosfonáty farmakologie   MeSH
• Papillomaviridae MeSH
• SLC transportéry biosyntéza   MeSH
• uridintrifosfát biosyntéza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• cidofovir MeSH
• cytidintrifosfát MeSH
• cytidylate kinase MeSH Prohlížeč
• cytosin MeSH
• nukleosidmonofosfátkinasa MeSH
• organofosfonáty MeSH
• SLC transportéry MeSH
• uridintrifosfát MeSH

ATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively efflux various xenobio-tics from the cells across the cell membrane and decrease a drugs efficiency. Lung cancer is the leading cause of death among all types of cancer in the Czech Republic, and its incidence is still rising. Ciglitazone, rosiglitazone and troglitazone belonging to PPARγ agonist family (formerly used in diabetes mellitus treatment) were selected to investigate their capability to influence expression of ABC transporters on lung cancer cells. Therefore, the effect of PPARγ of agonists on transcription of following ABC transporters was investigated: multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). We have investigated if these PPARγ agonists are substrates of ABC transporters using HL60 and HL60 derived cell lines (HL60-MDR1, HL60-MRP1, PLB-BCRP) by cytotoxicity test WST-1. We have mapped the changes in mRNA expression level of those transporters in A549 and HEK293 cells after PPARγ agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPARγ agonists serve as substrates to at least one ABC transporter under study. PPARγ activation correlates with up-regulation of PTEN which may modulate the expression of ABC transporters through PI3K/ Akt signaling pathway. We have shown that rosiglitazone and troglitazone inhibit mRNA expression of MDR1 transporter in both cell lines whereas the expression of MRP1 in HEK293 cell was up-regulated after rosiglitazone treatment and the expression of MDR1 was upregulated after ciglitazone treatment.

• MeSH
• ABC transportéry biosyntéza   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• thiazolidindiony farmakologie   MeSH
• transkriptom MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• thiazolidindiony MeSH

Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.

• MeSH
• ABC transportéry biosyntéza   genetika   metabolismus   MeSH
• embryonální vývoj genetika   fyziologie   MeSH
• exprese genu MeSH
• játra embryologie   MeSH
• ledviny embryologie   MeSH
• lidé MeSH
• mnohočetná léková rezistence MeSH
• P-glykoproteiny biosyntéza   genetika   metabolismus   MeSH
• střeva embryologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• P-glykoproteiny MeSH

The aim of our study was to evaluate the impact of acetylcholinesterase reactivators--K027 [1-(4-carbamoyl pyridinium)-3-(4-hydroxyiminomethyl pyridinium) propane dibromide], HI-6 [1-(4-carbamoylpyridinium)-3-(2-hydroxyimino methylpyridinium) oxapropane dichloride] and obidoxime [1,3-bis(4-hydroxyiminomethyl pyridinium)oxapropane dichloride] on hepatic functions in vivo. Male Wistar rats were randomly divided to seven groups and intramuscularly administered with saline and acetylcholinesterase reactivators (K027, HI-6 and obidoxime) at doses of 5% LD(50) and 50% LD(50). Liver tissue samples were taken 24 hr after administration. Histochemical detection of lipid droplets and immunohistochemical detection of multidrug resistance protein 2 (Mrp2) were provided. Lipid droplet count in rat liver did not show any significant differences in animals administered with K027, HI-6 and obidoxime in comparison with the control group. Mrp2 protein expression significantly decreased when animals were administered with K027 at a dose of 50% LD(50) and HI-6 and obidoxime at doses of 5% LD(50) and 50% LD(50), when compared to the controls. No statistical differences of Mrp2 expression were measured when animals were administered with K027 at a dose of 5% LD(50) in comparison with control animals. We found impaired hepatic transporter function after administration of HI-6, obidoxime and higher concentration of K027, which might be the underlying mechanism of acetylcholinesterase reactivators' hepatotoxicity.

• MeSH
• ABC transportéry biosyntéza   MeSH
• játra účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• LD50 MeSH
• metabolismus lipidů účinky léků   MeSH
• obidoxim chlorid chemie   toxicita   MeSH
• oximy chemie   toxicita   MeSH
• potkani Wistar MeSH
• pyridinové sloučeniny chemie   toxicita   MeSH
• reaktivátory cholinesterasy chemie   toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• ztučnělá játra chemicky indukované   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide MeSH Prohlížeč
• ABC transportéry MeSH
• Abcc2 protein, rat MeSH Prohlížeč
• asoxime chloride MeSH Prohlížeč
• obidoxim chlorid MeSH
• oximy MeSH
• pyridinové sloučeniny MeSH
• reaktivátory cholinesterasy MeSH

P-glycoprotein (P-gp) is a drug efflux transporter that limits the entry of various potentially toxic drugs and xenobiotics into the fetus and is thus considered a placental protective mechanism. In this study, P-gp expression was investigated in the rat chorioallantoic placenta over the course of pregnancy. Three methods have been employed: real-time RT-PCR, western blotting and immunohistochemistry. The expression of mdr1a and mdr1b genes was demonstrated as early as on the 11th gestation day (gd) and increased with advancing gestation. Western blotting analysis revealed the presence of P-gp in the rat placenta starting from gd 13 onwards. P-gp was localized in the developing labyrinth zone of the placenta on gd 13; from gd 15 up to the term P-gp was seen as a dot like continuous line in the syncytiotrophoblast layers. Our data confirm the presence of P-gp in the rat chorioallantoic placenta starting soon after its development, which may signify the involvement of P-gp in transplacental pharmacokinetics during the whole period of placental maturing.

• MeSH
• ABC transportér, podrodina B, člen 4 MeSH
• ABC transportéry biosyntéza   genetika   MeSH
• chorion metabolismus   MeSH
• imunohistochemie MeSH
• krysa rodu Rattus MeSH
• membrány účinky léků   metabolismus   MeSH
• messenger RNA biosyntéza   MeSH
• monoklonální protilátky MeSH
• P-glykoprotein biosyntéza   MeSH
• P-glykoproteiny biosyntéza   genetika   MeSH
• placenta metabolismus   MeSH
• placentace MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• těhotenství u zvířat metabolismus   MeSH
• těhotenství MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• messenger RNA MeSH
• monoklonální protilátky MeSH
• multidrug resistance protein 3 MeSH Prohlížeč
• P-glykoprotein MeSH
• P-glykoproteiny MeSH