Analysis of T cell receptor β chains in rat thymus,and rat Cα and C β sequences

In development, T cells first express their antigen receptors in the thymus, where they may undergo selection processes leading to major histocompatibility complex (MHC) restriction and tolerance. A high proportion of thymocytes are thought to fail this selection in some way and to be destined for intrathymic death. These cells are categorized as the cortical type since they constitute most of the cortical cells; they express both CD4 and CD8 antigens but only very low levels of MHC class I antigens. One suggested cause of thymocyte death is a failure to produce a functional T cell receptor (Tcr) due to errors in the rearrangements of germline DNA, resulting in V regions being absent or incorrectly spliced to the other segments of the transcribed gene. We have sequenced from the C region through to the V region of 14 rat Tcr chain clones isolated from thymocyte cDNA libraries. Of the 14, 13 have complete and correct rearrangements, whereas one was expressed from an unrearranged gene. Most of these clones are likely to be derived from the cortical population, for Northern blot analysis showed that these cells and total thymocytes expressed similar amounts of chain mRNA.Furthermore, the RNA from cortical-type cells contained a very similar ratio of full-length to truncated chain mRNA as did activated thymocytes and mature T lymphocytes. The data imply that defective chain gene rearrangement is not a major cause of failure in the selection of thymocytes. The sequences of the rat Tcr and chain constant regions are also reported.     

Variant RONΔ160 of the RON receptor tyrosine kinase promotes the growth and invasion in vitro and in vivo in gastric cancer cell lines

Background

Recepteur d’origine nantais (RON) is a receptor tyrosine kinase whose overexpression has been observed in human gastric cancers. This study aimed to determine whether overexpression of the variant RONΔ160 could induce tumorigenicity of gastric cancer cells in vitro or in vivo, and whether its specific small molecule inhibitor (Compound I) could inhibit the effect of RONΔ160.

Methods

We constructed human gastric cancer cell line MGC-803 that was stably transfected with a recombinant plasmid expressing RONΔ160, and the effect of RONΔ160 overexpression and macrophage-stimulating protein (MSP) activation on proliferation, migration and invasion abilities of MGC-803 cells were evaluated. Tumor-bearing mice with gastric cancer cells were used to analyze the effects of RONΔ160 overexpression and Compound I on implanted tumor growth.

Results

In vitro, overexpression of RONΔ160 in MGC-803 cells resulted changes to their cell morphology, and promoted cell proliferation, migration and invasion. In addition, overexpression of RONΔ160 increased the proportion of cells in the S phase. The effect of RONΔ160 was significantly enhanced by induction of MSP inducing (p < 0.05). In vivo, RONΔ160 promoted the growth of MGC-803 cells in nude mice, including increased tumor size and weight, and lower tumor incubation period. The Compound I inhibited the tumorigenic abilities of RONΔ160 (p <0.05).

Conclusions

The results indicate that overexpression of the variant RONΔ160 altered the phenotype and tumorigenicity of MGC-803 cells. Its specific small molecule inhibitor could inhibit the effect of RONΔ160. Therefore, the variant RONΔ160 may become a potential therapeutic target for gastric cancer.     

Analysis of the intracellular localization of p73 N-terminal protein isoforms TAp73 and ∆Np73 in medulloblastoma cell lines

The protein homologous to the tumor suppressor p53, p73, has essential roles in development and tumorigenesis. This protein exists in a wide range of isoforms with different, even antagonistic, functions. However, there are virtually no detailed morphological studies analyzing the endogenous expression of p73 isoforms at the cellular level in cancer cells. In this study, we investigated the expression and subcellular distribution of two N-terminal isoforms, TAp73 and ΔNp73, in medulloblastoma cells using immunofluorescence microscopy. Both proteins were observed in all cell lines examined, but differences were noted in their intracellular localization between the reference Daoy cell line and four newly established medulloblastoma cell lines (MBL-03, MBL-06, MBL-07 and MBL-10). In the new cell lines, TAp73 and ΔNp73 were located predominantly in cell nuclei. However, there was heterogeneity in TAp73 distribution in the cells of all MBL cell lines, with the protein located in the nucleus and also in a limited non-random area in the cytoplasm. In a small percentage of cells, we detected cytoplasmic localization of TAp73 only, i.e., nuclear exclusion was observed. Our results provide a basis for future studies on the causes and function of distinct intracellular localization of p73 protein isoforms with respect to different protein–protein interactions in medulloblastoma cells.     

Analysis of β-globin gene haplotypes in Asian Indians: origin and spread of β-thalassaemia on the Indian subcontinent

-globin gene haplotypes were determined for 196 normal (-A) and 419 thalassaemia (-Th) chromosomes of individuals from four different regions of the Indian subcontinent; North-west Pakistan, Gujarat, Punjab and Sindh. Analysis of -A and -Th haplotypes and haplotype-mutation associations in each regional group along with a consideration of Indian history provided information about the origin and spread of -thalassaemia mutations on the Indian subcontinent. The data are consistent with relatively recent and local origins for most -thalassaemia mutations. The frequencies of particular alleles differ markedly in various regions and these may be useful population markers. Of the high frequency alleles, intervening sequence 1 (IVS-1) nucleotide 5 (G-C) and codons 41/42 (-CTTT) appear to be older as suggested by multiple haplotype associations and a widespread geographical distribution. The microepidemiology of -thalassaemia in this region reflects considerable ethnic diversity, gene flow from population migration and natural selection by malaria infection.     

Relative biological effectiveness of 25 and 10 kV X-rays for the induction of chromosomal aberrations in two human mammary epithelial cell lines

Administration of ionizing radiation for diagnostic purposes can be associated with a risk for the induction of tumors. Therefore, particularly with regard to general screening programs, e.g. with mammography, cost-benefit considerations must be discussed including risk estimation depending upon the radiation quality administered. The present study was initiated to investigate the in vitro X-ray energy dependence for the induction of chromosomal aberrations in the two mammary epithelial cell lines, 184A1 and MCF-12A. The induced excess fragments, dicentric chromosomes and centric rings were analyzed and the relative biological effectiveness (RBE) was determined for 10 and 25 kV X-rays relative to 200 kV X-rays. The assumed energy dependence with higher values for 10 kV X-rays was confirmed for the excess fragments, with RBE_M values of 1.92 ± 0.26 and 1.40 ± 0.12 for 10 kV X-rays and 1.17 ± 0.12 and 0.97 ± 0.10 for 25 kV photons determined for cell lines 184A1 and MCF-12A, respectively. Meaningful results for the induction of dicentric chromosomes and centric rings were obtained only for higher doses with RBE values of 1.31 ± 0.21 and 1.70 ± 0.29 for 184A1 and 1.08 ± 0.08 and 1.43 ± 0.12 for MCF-12A irradiated with 25 and 10 kV X-rays, respectively.     

Description of the oöcysts of two new species of Eimeria (Apicomplexa: Eimeriidae) from the rough earth snake Virginia striatula (Serpentes: Colubridae) in Texas and Arkansas

Coccidian oöcysts recovered from the faeces of rough earth snakes Virginia striatula (Serpentes: Colubridae) were found to represent two previously unreported eimerians. Oöcysts of Eimeria desotoensis n. sp. were found in 5/32 (16%) of the snakes and were spherical to ellipsoidal, 18.4 × 17.2 (15–21.5 × 15–19.5) μm, with a thin, single-layered wall; their shape-index (length/width) was 1.07 (1.00–1.23). A micropyle and oöcyst residuum were absent; polar granule were present in 33% of the oöcysts. The sporocysts were ovoidal, 11.5 × 7.6 (10.5–13 × 7–8) μm, with a Stieda body; their shape-index was 1.51 (1.30–1.68). The sporocyst residuum was moderate in size and composed of a cluster of granules. Oöcysts of Eimeria hobartsmithi n. sp. were found in 2/32 (6%) of the snakes and were subspherical to ellipsoidal, 18.0 × 15.7 (16–20 × 15–17) μm, with a thin, single-layered wall; their shape-index was 1.15 (1.02–1.32). A micropyle, oöcyst residuum and polar granule were absent. The sporocysts were elongate, 13.2 × 6.3 (12–14.5 × 6–6.5) μm, with a Stieda body; their shape-index was 2.10 (1.88–2.34). A large sporocyst residuum was present in each sporocyst, often obscuring the sporozoites. In addition to the two new species, oöcysts of E. striatula Upton & McAllister, 1990 were observed in 38% of the snakes.     

Inhibition of protein synthesis enhances the lytic effects of tumor necrosis factor α and interferon γ in cell lines derived from gynecological malignancies

Summary Few clinical responses have occurred in preliminary studies using the cytokines tumor necrosis factor (TNF) or interferon (IFN) in cancer patients. This may be related to the observation that many malignant cell lines are resistant to lysis by these cytokinesin vitro. Resistance to lysis by TNF or IFN in many cells is controlled by a protein-synthesis-dependent mechanism, such that when protein synthesis is inhibited cells become sensitive to lysis by these cytokines. Because there is some evidence that TNF and IFN act through different lytic mechanisms and are opposed by different resistance mechanisms, we treated a panel of eight cell lines, five derived from human cervical carcinomas (ME-180, MS751, SiHa, HT-3, and C-33A) and three derived from ovarian carcinomas (Caov-3, SK-OV-3, and NIH: OVCAR-3) with both TNF and IFN to determine whether such combination treatment might maximizein vitro cell lysis. Our results showed that pretreatment with IFN followed by exposure to TNF in the presence of protein synthesis inhibitors increased lysis of seven of the eight cell lines above that seen with either TNF or IFN and inhibitors of protein synthesis. Only the cell line C-33A was resistant to lysis by TNF and IFN, when exposed to these agents both alone and in combination with protein synthesis inhibitors. Clinically, combining the cytokines TNF and IFN with protein synthesis inhibitors may maximize thein vivo lytic effects of these cytokines.Supported by American Cancer Society Career Development Award 90-221     

δ1-Pyrroline-5-carboxylate reductase as a new target for therapeutics: inhibition of the enzyme from Streptococcus pyogenes and effects in vivo

Compounds able to interfere with amino acid biosynthesis have the potential to inhibit cell growth. In both prokaryotic and eukaryotic microorganisms, unless an ornithine cyclodeaminase is present, the activity of δ¹-pyrroline-5-carboxylate (P5C) reductase is mandatory to proline production, and the enzyme inhibition should result in amino acid starvation, blocking in turn protein synthesis. The ability of some substituted derivatives of aminomethylenebisphosphonic acid and its analogues to interfere with the activity of the enzyme from the human pathogen Streptococcus pyogenes was investigated. Several compounds were able to suppress activity in the micromolar range of concentrations, with a mechanism of uncompetitive type with respect to the substrate P5C and non-competitive with respect to the electron donor NAD(P)H. The actual occurrence of enzyme inhibition in vivo was supported by the effects of the most active derivatives upon bacterial growth and free amino acid content.     

A new genus and two new species of trypanorhynch cestodes (Tentaculariidae) from the sharks Carcharhinus sorrah (Müller & Henle) and Sphyrna lewini (Griffith & Smith) from off the coasts of Malaysia and Mexico

Two new tentaculariid species were found infecting carcharhiniform sharks from off the coasts of Malaysian Borneo and the southwestern coast of the Baja California Sur, Mexico. Both new species exhibit a homeoacanthous heteromorphous basal and a homeoacanthous homeomorphous metabasal armature. Since this hook arrangement is unique within the tentaculariids and the taxonomy in this group deeply depends on the tentacular armature, Reimeriella n. g. is erected to accommodate R. varioacantha n. sp. ex Carcharhinus sorrah (Müller & Henle) and R. mexicoensis n. sp. ex Sphyrna lewini (Griffith & Smith). Unlike R. mexicoensis n. sp., R. varioacantha n. sp. has a pars bothrialis not overlapping the pars bulbosa and the number of testes is higher. Reimeriella mexicoensis n. sp. possesses very large uncinate to falcate hooks in the basal armature, while in R. varioacantha n. sp. these hooks are almost the same in size as the remaining hooks in both the basal and metabasal armature. The latter species is the first tentaculariid species where the metabasal armature very closely resembles an eutetrarhynchid with a heteroacanthous typical homeomorphous metabasal armature and a high number of spiniform hooks per half spiral row (10–11 vs 6–7 in R. mexicoensis n. sp.) in the metabasal and apical armature. This pattern provides further morphological evidence for the close relationship of the Eutetrarhynchoidea and the Tentacularioidea. Reimeriella varioacantha n. sp. enriches the trypanorhynch fauna from off the coast of Malaysian Borneo while R. mexicoensis n. sp. is a novel record of a tentaculariid trypanorhynch from the Mexican Pacific.

     

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.     

Recombinant human interferon γ exerts an anti-proliferative effect and modulates the expression of human leukocyte antigens A,B,C and DR in human urothelial cell lines

Summary In this study we have treated three malignant (TGrIII) and two pre-malignant (TGrII) urothelial cell lines with recombinant human interferon (rHu-INF). The malignant cells (HCV29-T112C1, Hu1703He and T24) were inhibited in growth by more than 50% after treatment with 100–1000 units of rHu-INF/ml for 4 days as compared to untreated controls. The growth of the pre-malignant cell lines (HCV29 and Hu609) was not influenced to the same extent in the presence of rHu-INF in the culture medium. Treatment with rHu-INF increased the expression of monomorphic human leukocyte antigens (HLA) A,B,C as well as ₂-microglobulin in all the cell lines tested, as demonstrated using a quantitative immunofluorescence assay. The tumourigenic cell lines increased their expression of HLA in a dose-dependent way, whereas treatment of the non-tumourigenic cells with higher concentrations of rHu-INF than 10 units/ml, did not increase the HLA-A,B,C expression further. None of the cell lines expressed HLA-DR unless treated with rHu-INF. No correlation between tumourigenicity and the dose of rHu-INF required for de novo induction of HLA-DR could be demonstrated. After removal of rHu-INF from the medium, the expression of HLA-DR gradually decreased in less than 14 days, indicating that the expression of HLA-DR is not constitutive but dependent upon the presence of rHu-INF. We conclude that human urothelial cells grown in vitro are sensitive to the anti-proliferative and major-histocompatibility-complex-modulating effects of rHu-INF, and that malignant urothelial cells are more sensitive than pre-malignant cells. Finally, our data indicate a possible role for rHu-INF in the management of human bladder cancer.     

Pseudohypoparathyroidism type Ia: two new heterozygous frameshift mutations in exons 5 and 10 of the Gsα gene

Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease characterized by resistance to PTH and other hormones that act via cAMP. Patients have deficient activity of Gs, the subunit of the G protein, which couples hormone receptors to stimulation of adenylate cyclase. We describe two new mutations discovered in two sporadic patients with PHP-Ia. Using genomic DNA, we have amplified exons 2–13 of the Gs gene (GNAS1) by PCR, and sequenced the resulting products. Both patients had Albright's hereditary osteodystrophy, resistance to multiple hormones, and deficient Gs activity. In the first patient, a deletion of a C in exon 5 at codon 115 was found. In the second patient, an insertion of a C in exon 10 at codon 267 was detected. Both these heterozygous mutations cause frameshift, and predict decreased production of Gs. This report adds two new Gs mutations to the known ten mutations recently described.     

Generation of new transposons in vivo: an evolutionary role for the “staggered” head-to-head dimer and one-ended transposition

From a plasmid carrying the tnpA gene and one inverted repeat sequence (IR) of transposon Tn3, plasmids containing a structure characteristic of transposons, i.e., two IRs flanking a tnpA gene, were generated spontaneously in vivo. They appear to have arisen either through the formation of a “staggered” head-to-head dimer or by so-called one-ended transposition. These putative transposons could indeed transpose to, or form cointegrates with, a recipient plasmid. Based on these findings it is proposed that a primeval transposase gene and its target site evolved first, and subsequently gave rise to a “fully-fledged” transposon by head-to-head dimerization or one-ended transposition. Received: 30 October 1998 / Accepted: 1 April 1999     

Plant species microendemism and conservation of montane maquis in New Caledonia: two new species of Pancheria (Cunoniaceae) from the Roche Ouaïème

Two species of Pancheria (Cunoniaceae) described here, Pancheria minima J.C. Bradford and Pancheria ouaiemensis J.C. Bradford, draw attention to a recently recognized biodiversity pattern in New Caledonia. Montane maquis on acidic substrates, especially on the Roche Ouaïème, harbors numerous endemic species and is a rare and globally unique ecosystem. We cite 12 species, most described in the past several years, known only from the Roche Ouaïème in an area less than 10km². Overall, 27 species are known only from montane maquis and currently not found in a well-protected area. The major local threat to montane maquis habitat is anthropogenic fire, with climate change a possible long-term problem. Those montane maquis species known from one or two localities, occupying very small areas, and with declining habitat quality are critically endangered or endangered based on IUCN Red List criteria. Adding the Roche Ouaïème to the reserve system of New Caledonia is recommended to protect and manage a representative area of montane maquis on acidic substrates. A research strategy is proposed to identify species most at risk, locate possible unknown areas of montane maquis, and update taxonomic knowledge. A review of characters that vary among Pancheria species is provided, and the inflorescence architecture is described and diagramed. Both new Pancheria species occur at upper elevations in shrubby habitats. P. minima is remarkable in that the size of plants, leaves and reproductive parts is highly reduced compared to other known species.     

Retinoic acid receptor isoform RARγ 1: an antagonist of the transactivation of the RARβ RARE in epithelial cell lines and normal human keratinocytes

The diversity of isoforms of retinoic acid (RA) receptors (RARs) and of DNA sequences of retinoic acid-responsive elements (RAREs) suggests the existence of selectivities in the RAR/RARE recognition or in the subsequent gene modulation. Such selectivities might be particularly important for RAREs involved in positive feedback, eg. the RAR RARE. In the present work we found that in several epithelial cell lines, reporter constructs containing the RAR RARE linked to the HSV-tk promoter were transactivated in the presence of RA by endogenous RARs and co-transfected RAR₁ and RAR₂ isoforms, but not by RAR₁. On the contrary, this latter isoform behaved towards the RAR RARE as an inhibitor of the transactivation produced by endogenous RARs and by cotransfected RAR₁ and RAR₂. RAR₁ also behaved as an antagonist of the transactivation produced by cotransfected RXR. The natural RAR gene promoter or RAR RARE tk constructs were not activated by the endogenous receptors of normal human keratinocytes (NHK), which are known to contain predominantly RAR₁. It was, however, possible to activate to a certain extent RAR RARE-reporter constructs in NHK by co-transfecting RAR₁, RAR₂ or RXR. The antagonist behavior of RAR₁ towards the RAR RARE may explain why in certain cell types such as keratinocytes, RAR is neither expressed nor induced by RA.Abbreviations DMEM Dulbecco's modified Eagle medium - DMSO dimethyl sulfoxide - FCS fetal calf serum - MEM minimal Eagle medium - NHK normal human keratinocyte - RA retinoic acid - RAR retinoic acid receptor - RARE retinoic acid responsive element - TRE thyroid responsive element - VDRE vitamin D response element - RXR retinoid X receptor     

Socioeconomic status and cancer survival in Brazil: Analysis of population data from the municipalities of Aracaju and Curitiba, 1996–2012

IntroductionThe association between socioeconomic status and cancer prognosis has been demonstrated in several countries. Despite the existence of indirect evidence of this phenomenon in Brazil, few studies in this regard are available.ObjectivesThe objective of the present study is to analyse socioeconomic related survival gaps for patients diagnosed with breast, cervical, lung, prostate, and colorectal cancer in the cities of Aracaju (SE) and Curitiba (PR).MethodsUsing population-based data, we estimated net survival by tumour site, year of diagnosis, socioeconomic status and local of residence. Net survival estimation was done with multilevel parametric model allowing flexible spline functions do estimate excess mortality hazards.Results28,005 cases were included in survival analysis. Five-year net survival showed positive association with SES. Intermunicipal survival gaps favouring Aracaju where prominent for breast (reaching 16,1% in 5 years)ObjectivesStudy the impact of socioeconomic factors on cancer survival in two Brazilian capitals. Methods: Survival analysis using population-based cancer data including patients diagnosed with breast, lung, prostate, cervical and colorectal cancer between 1996 and 2012 in Aracaju and Curitiba. Outcomes were excessive mortality hazard (EMH) and 5- and 8-years net survival (NS). The association of race/skin color and socioeconomic level (SES) with EMH and net survival were analyzed using a multilevel regression model with flexible splines.Results28,005 cases were included, 6636 from Aracaju and 21,369 from Curitiba. NS for all diseases studied increased more prominently for Curitiba population. We observed NS gap between the populations of Aracaju and Curitiba that increased or remained stable during the study period, with emphasis on the growth of the difference in NS of lung and colon cancer (among men). Only for cervical cancer and prostate cancer there was a reduction in the intermunicipal gaps. 5-year NS for breast cancer in Aracaju ranged from 55.2% to 73.4% according to SES. In Curitiba this variation was from 66.5% to 83.8%.ConclusionThe results of the present study suggests widening of socioeconomic and regional inequalities in the survival of patients with colorectal, breast, cervical, lung and prostate cancers in Brazil during the 1990 s and 2000 s     

Making Sense in Time: Remote Sensing and the Challenges of Temporal Heterogeneity in Social Analysis of Environmental Change—cases from Malawi

This article contributes to the encouraging recent trend toward more critical examination of the linkages between remote sensing and social analysis of environmental change. Using two case studies from Malawi, we explain the importance of thinking about temporal scale when using remote sensing data. Specifically, from our on-the-ground research, we came to appreciate three important issues: (1) multiple causation and multiple temporal scales operating simultaneously—making inference of casual relations between particular social factors and observed land use changes difficult; (2) ‘visible’ vs. ‘invisible’ processes and events; and (3) ‘continuous’ vs. ‘punctuated’ social and environmental processes. We observe that in each case, social differentiation is key to understanding which temporal frames are most relevant in understanding observed land use dynamics. We conclude that, while these are not entirely new observations, research on the applications of remote sensing in social analysis of environmental change could be enriched by more rigorous examination of linkages between environmental change, temporal scale, and the social relations (including social differentiation) that can help to explain how and why particular temporal frames are most salient.

Expression, localization, and inducibility by bile acids of hepatobiliary transporters in the new polarized rat hepatic cell lines, Can 3−1 and Can 10

Sinusoidal and apical transporters are responsible for the uptake and biliary elimination of many compounds by hepatocytes. Few in vitro models are however available for analyzing such functions. The expression and bile-acid inducibility of 13 transporters and two nuclear receptors were investigated in the new rat polarized lines, Can 3−1 and Can 10, and in their unpolarized parent, Fao. The relative abundance of mRNA, the protein level, and their localization were examined by real-time quantitative PCR, Western blotting, immunofluorescence, and confocal microscopy. Compared with rat liver, mRNA levels of Fao cells were: negligible for Bsep/Abcb11; lower for the uptake transporters Ntcp and Oatps; similar for SHP, FXR, and Bcrp/Abcg2; and higher (four–fold to 160-fold) for the efflux pumps Mdr1b/Abcb1b, Mdr2/Abcb4, Mrp1/Abcc1, Mrp2/Abcc2, Mrp3/Abcc3, Abcg5, and Abcg8. This profile was mostly maintained (and improved for Bsep) in Can 10. Some transporters were less well expressed in Can 3−1. In both lines, sinusoidal (Ntcp, Mrp3) and canalicular transporters (Mdr-P-glycoproteins detected with C219 antibody, Mrp2) were localized at their correct poles. Bile-acid effects on polarity and mRNA levels of transporters were analyzed after a 6-day treatment with 50 μM taurocholic, chenodeoxycholic (CDCA), or ursodeoxycholic acid (UDCA). No polarization of Fao cells was induced; Can 10 and Can 3−1 polarity was maintained. CDCA and UDCA induced marked enhancement of the volume of Can 10 bile canaliculi. CDCA upregulated Bsep, Mdr2, SHP, Mdr1b, and Oatp2/1a4 in Can 10 (two- to seven-fold) and in Fao cells. Thus, Can 10 constitutes an attractive polarized model for studying vectorial hepatobiliary transport of endogenous and xenobiotic cholephilic compounds. This work was supported by a grant from Egide (PAI Picasso) and the Acción Integrada Hispano-Francesa (HF2003-0089). This research group is part of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministerio de Educación y Ciencia, Spain and the European Regional Development Fund (ERDF; grant BFU2005-24983-E/BFI) and belongs to the “Centro de Investigación Biomédica en Red” for Hepatology and Gastroenterology Research (CIBERehd), Instituto de Salud Carlos III, Spain.