Biomedical subjects

N Miwa

Publications and source records attributed to N Miwa.

At least 19 recordsLinked to original sources

PubMed2006

Promotive effects of hyperthermia on the inhibition of DNA synthesis in ehrlich ascites tumor cells by eicosapentaenoic and docosahexaenoic acids.

AIM: To evaluate inhibitory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on DNA synthesis in combination with hyperthermia in vitro. METHODS: A suspension of Ehrlich ascites tumor cells (EAT) was mixed with DHA or EPA in a glass tube, heated at 37 degrees C, 40 degrees C, or 42 degrees C for 1 h in a water bath, and cultured at 37 degrees C for 19 or 96 h. DNA synthesis was assayed by monitoring of the incorporation of [3H]-thymidine into the acid-insoluble fraction. DHA or EPA incorporated into EAT cells was extracted and measured by thin-layer chromatography and gas-liquid chromatography. RESULTS: The inhibition of DNA synthesis by EPA or DHA increased markedly upon the treatment at 42 degrees C and 40 degrees C compared to that at 37 degrees C. At 37 degrees C, inhibitory action of EPA was more potent than that of DHA at low concentrations (at 50 microM -- DNA synthesis level: EPA, 63.1%; DHA, 87.9%), whereas inhibitory action of DHA was higher at 150 muM (16.7%, 4.4%, ibid.). The effect of DHA compared to EPA was more marked at 40 degrees C (29.0%, 19.2% at 100 microM) or 42 degrees C (19.7%, 10.6% at 100 microM). Evaluation of DNA synthesis rate in the cells treated for 1 h by EPA or DHA with the next culturing of EAT cells for 19 h resulted in the enhanced inhibitory activity of EPA even at concentrations as low as 50 microM at either 37 degrees C (0.5%, 11.3%) or 42 degrees C (0.6%, 4.5%), which in these conditions was higher than that of DHA. At the same time the rate of incorporation of EPA in EAT cells at 37 degrees C or 42 degrees C was lower than that of DHA. CONCLUSION: Administration of DHA or EPA in vitro significantly inhibit DNA synthesis, and such effect is enhanced by combination of PUFAs with hyperthermia.

Animals↗

PubMed2002

Yersinia pseudotuberculosis infection in breeding monkeys: detection and analysis of strain diversity by PCR.

In the last three decades, several monkeys reared in outdoor/indoor-outdoor breeding colonies and cages of the Primate Research Institute, Kyoto University, died of yersiniosis caused by Yersinia pseudotuberculosis, necessitating introduction of a method to detect the bacteria rapidly and thus allow preventive measures to be undertaken. A rapid nested polymerase chain reaction (PCR) method for identification of Y. pseudotuberculosis in fecal samples and a random amplified polymorphic DNA (RAPD)-PCR approach for distinguishing between bacterial strains were therefore developed. Yersinia pseudotuberculosis isolates from monkey specimens were found to be classifiable into several types. To determine the source of infection, hundreds of fecal samples of wild rats, pigeons, and sparrows were collected from around the breeding colonies and cages, and subjected to PCR analyses. Yersinia pseudotuberculosis was detected in 1.7% of the fecal samples of wild rats. The DNA fingerprints of the bacteria revealed by RAPD-PCR were the same as that of one strain isolated from macaques, suggesting the wild rat to be a possible source of infection.

Adhesins, Bacterial↗

PubMed2002

Catheter dysfunction and thrombosis of double-lumen hemodialysis catheters placed in the femoral vein.

OBJECTIVE: Intraluminal thrombosis of the catheter was thought to be a major cause of catheter dysfunction. We evaluated if thrombi appear in the luminal side or outside of the catheters placed in the femoral vein in 21 hemodialysis patients. METHODS: 23 double-lumen catheter (25 cm long and 4 mm diameter polyurethane) strippings were consecutively performed. Mean catheter dwell time was 17.9 +/- 11.2 days (2-45 days). The femoral vein was observed with ultrasound echography, and thrombo-venous ratio (thrombus diameter/vein diameter) was calculated. X-rays were also taken to clearly visualize the thrombi followed by contrast medium injection through the catheter. RESULTS: Tube-shaped thrombi were echographically detected in 22 of 23 catheters (95.7%) when the catheter was stripped. Ten catheters (43.5%) were stripped due to the reduced blood flow, and tube-shaped thrombi were observed in the femoral vein, whereas no thrombus was found in the intraluminal side of the catheter. In 7 of 23 patients (30.4%) with leg edema on the same side of the catheter, the thrombovenous ratio was 78.9 +/- 7.4%, which was higher than that in the patients without leg edema (52.1 +/- 11.1%). CONCLUSION: The tube-shaped thrombi, formed around the double-lumen catheter, may cause catheter dysfunction and reduced venous return of the lower legs. The catheter should be removed as soon as thrombosis is diagnosed, especially when accompanied by leg edema.

Aged↗

PubMed2001

The relationship between UVB screening and cytoprotection by microcorpuscular ZnO or ascorbate against DNA photodamage and membrane injuries in keratinocytes by oxidative stress.

Decreased cell viability and increased formation of cyclobutane-type pyrimidine dimers (CPDs) in DNA of UVB-irradiated keratinocytes were shown to be appreciably restored by the addition of w/o emulsion of microcorpuscular zinc oxide (mcZnO) with a corpuscle diameter of 0.15 microm. The cytoprotection was exerted only by 20 wt/wt% mcZnO at levels equivalent to 40- to 100-microm-thick emulsion layers, which screened 90-92% of the incident UVB. However, protection was not seen by mcZnO below 20-microm thickness, which, unexpectedly, screened 79% of the incident radiation. This suggests that thorough UVB screening is necessary for cytoprotection. This may be attributable to involvement of intracellular reactive oxygen species (ROS) secondarily generated from UVB-irradiated mcZnO. Intracellular ROS was increased in mcZnO-added cells in a time-dependent manner even after UVB irradiation, contrasting with reduction of intracellular ROS in ascorbic acid-added cells. UVB-induced disruption of cell membrane integrity was reduced by mcZnO at 100-microm thickness, equivalent to the addition of ascorbic acid of 50 microM. Thus, mcZnO was thought to be cytoprotective through reductions of intracellular ROS generation, CPD formation and cell membrane disintegration when added so abundantly so as to achieve UVB-screening more than 90%.

Animals↗

PubMed2001

Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator.

We have previously reported that a heat-stable activator for ganglioside metabolism, G(M2) activator, potently stimulates ADP-ribosylation factor (ARF)-dependent phospholipase D (PLD) activity (presumably PLD1) in an in vitro system [Nakamura, Akisue, Jinnai, Hitomi, Sarkar, Miwa, Okada, Yoshida, Kuroda, Kikkawa and Nishizuka (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 12249-12253]. However, little is known about the regulation of PLD2. In the present studies we have investigated the regulation of PLD2 by G(M2) activator and various other regulators including ARF. PLD2 was potently stimulated in vitro by G(M2) activator in a time- and dose-dependent manner. Neither ARF nor protein kinase C caused any significant changes in PLD2 activity. Importantly, PLD2 responsiveness to ARF was greatly enhanced by G(M2) activator, suggesting a possible role for G(M2) activator as a coupling factor. G(M2) activator was also demonstrated to physically associate with PLD2 in a stoichiometric manner. Further, PMA stimulation of COS-7 cells overexpressing both G(M2) activator and PLD2 resulted in a marked increase in the association of the two molecules. Interestingly, ARF association with PLD2 was greatly increased by G(M2) activator. Moreover, G(M2) activator enhanced PMA-induced PLD activity in a synergistic manner with ARF in streptolysin-O-permeabilized, cytosol-depleted HL-60 cells, suggesting that G(M2) activator may regulate PLD in a concerted manner with other factors, including ARF, inside the cells.

Amino Acid Sequence↗

PubMed2001

Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis.

To elucidate the molecular mechanism of colorectal carcinogenesis, we have been attempting to isolate genes involved in the beta-catenin/T-cell factor pathway. In the experiments reported here, analysis by cDNA microarray indicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta-catenin. Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition. Our results suggest that the AF17 gene product is likely to be involved in the beta-catenin-T-cell factor/lymphoid enhancer factor signaling pathway and to function as a growth-promoting, oncogenic protein. These findings should aid development of new strategies for diagnosis, treatment, and prevention of colon cancers and acute leukemias by clarifying the pathogenesis of these conditions.

3T3 Cells↗

PubMed2001

An outbreak of food poisoning due to egg yolk reaction-negative Staphylococcus aureus.

An outbreak of staphylococcal food poisoning due to an egg yolk (EY) reaction-negative strain occurred in Japan. Twenty-one of 53 dam construction workers who ate boxed lunches prepared at their company cafeteria became ill, and eight required hospital treatment. The outbreak showed a typical incubation time (1.5-4 h with a median time of 2.7 h) and symptoms (vomiting and diarrhea) of staphylococcal food poisoning. Staphylococcus aureus, which produces staphylococcal enterotoxin (SE) A, was isolated from four fecal specimens of eight patients tested. Scrambled egg in the boxed lunches contained 20-40 ng/g of SEA, and 3.0 x 10(9)/g of viable S. aureus cells that produced this toxin. All isolates from patients and the food were EY reaction-negative, coagulase type II, and showed the same restriction fragment length polymorphism (RFLP) pattern. We concluded that the outbreak was caused by scrambled egg contaminated with EY reaction-negative S. aureus. In Japan, outbreaks of staphylococcal food poisoning are mainly caused by EY reaction-positive S. aureus, and EY reaction-negative colonies grown on agar plates containing EY are usually not analyzed further for detection of S. aureus. The present outbreak suggested that EY reaction-negative isolates should be subjected to further analysis to detect the causative agents of staphylococcal food poisoning.

Disease Outbreaks↗

PubMed2001

Calcium-binding by p26olf, an S100-like protein in the frog olfactory epithelium.

Frog p26olf is a novel S100-like Ca2+-binding protein found in olfactory cilia. It consists of two S100-like domains aligned sequentially, and has a total of four Ca2+-binding sites (known as EF-hands). In this study, to elucidate the mechanism of Ca2+-binding to each EF-hand (named EF-A, -B, -C and -D from the N-terminus of p26olf), we examined Ca2+-binding in wild-type p26olf and also in its mutants in which a glutamate at the -z coordinate position within each Ca2+-binding loop was substituted for a glutamine. Flow dialysis experiments showed that the wild-type binds nearly four Ca2+ per molecule maximally, while all the mutants bind approximately three Ca2+. Although EF-B and -D are p26olf-specific EF-hands and their role in Ca2+-binding is not known, the result unequivocally showed that they actually bind Ca2+. The overall Ca2+-binding affinity decreased in the three mutants. The decrease was very large in the mutants of EF-A and -B, which suggested that the Ca2+-affinities are high in EF-A and -B in the wild-type. Assuming the presence of four steps of Ca2+-binding, we determined the dissociation constant of each step in wild-type p26olf. To assign which step takes place at which EF-hand, we measured the antagonistic effect of K+ on each step, as the effect of K+ is thought to be a function of the number of the carboxyl groups in an EF-hand. Although the actual Ca2+-binding mechanism may not be so simple, this study together with the mutation study suggested a tentative Ca2+-binding model of p26olf: the order of Ca2+-binding to p26olf is EF-B, EF-A, EF-C and EF-D. Based on these results, we speculate that similar Ca2+-binding takes place in an S100 dimer.

Amino Acid Motifs↗

PubMed2001

The influence of rearing conditions on the physical growth of captive Japanese macaques (Macaca fuscata).

To clarify the influence of rearing conditions on the growth of various body parts of Japanese macaques (Macaca fuscata), two groups reared under different conditions, i.e., a group born and reared in open enclosures (Enclosure group) and another consisting of macaques born and reared in cages (Caged group), were somatometrically analyzed. Somatometric data on 36 measures of various body parts were collected from 77 males and 92 females. Growth in many body parts was smaller in the Caged group than in the Enclosure group. Body parts that exhibited large incremental increases were more sensitive to differences in rearing space at the infantile growth stage in both sexes. Recovery from delayed growth at the pubertal growth stage was found in many body parts. However, the size of some locomotor elements such as the wrist and hand, and ankle and foot strongly reflected limitations of space and changes due to this were irreversible. Females were more sensitive than males to such differences in rearing conditions. We conclude that open enclosures with ample rearing space are necessary for the innate growth of Japanese macaques to occur.

Animal Husbandry↗

PubMed2001

Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers.

Accumulation of beta-catenin in cytoplasm and nuclei is frequently observed in a wide variety of tumors arising, for example, in the colon, liver, uterus, or brain. In association with Tcf/LEF transcription factors, beta-catenin regulates expression of genes involved in the Wnt/wingless signaling pathway, but the precise mechanisms are unclear. Here we report evidence that the claudin-1 (CLDNI) gene is one of the genes regulated by beta-catenin. Not only did expression of CLDN1 decrease significantly in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of wild-type APC into the APC-deficient colon cancer cells, but also two putative Tcf4 binding elements in the 5' flanking region of CLDN1 were confirmed to be responsible for activating its transcription. We documented increased expression of CLDN1 in all 16 primary colorectal cancers we examined, compared with adjacent noncancerous mucosae. Furthermore, immunohistochemical staining demonstrated that claudin-1 was weakly stained at apical boarder of lateral membrane of noncancerous epithelial cells and that it was strongly stained at all cell-cell boundaries and in the cytoplasms of cancer cells. Our results imply that claudin-1 is involved in the beta-catenin-Tcf/LEF signaling pathway, and that increased expression of claudin-1 may have some role in colorectal tumorigenesis.

Claudin-1↗

PubMed2000

Characterization of p26olf, a novel calcium-binding protein in the frog olfactory epithelium.

We have previously shown that p26olf is a novel S100-like Ca(2+)-binding protein in the frog olfactory epithelium. In this paper, we characterized the Ca(2+) binding property of p26olf, examined the precise localization in the frog olfactory epithelium, and searched for the possible target proteins of p26olf. By flow dialysis experiments using (45)Ca, p26olf was suggested to bind approximately 4 Ca(2+). Circular dichroism measurement showed that binding of Ca(2+) to p26olf induces an increase in the apparent content of both alpha-helix and beta-sheet with an apparent K(d) value of 2.4 micrometer. Electron microscopic observation disclosed p26olf immunoreactivity in the cilia, dendritic knob, and dendrite of olfactory receptor cells. Blot overlay analysis and affinity purification of p26olf-binding proteins showed that p26olf binds to a frog beta-adrenergic receptor kinase-like protein in a Ca(2+)-dependent manner. These results suggested that p26olf has some roles in the olfactory transduction or adaptation.

Amphibian Proteins↗

PubMed2000

Isolation and characterization of a novel human gene, DRCTNNB1A, the expression of which is down-regulated by beta-catenin.

Beta-catenin plays significant roles in cell-to-cell adhesion and the Wnt/Wg signal transduction pathway. Accumulation of this protein in the cytoplasm and nucleus as a result of mutations of the adenomatous polyposis coli tumor suppressor gene or of the beta-catenin gene itself is often seen in a wide variety of tumors including carcinomas of the colon, liver, uterus, and brain. Interaction of accumulated beta-catenin with Tcf/Lef transcription factors is known to deregulate expression of some downstream genes, but the precise mechanisms whereby beta-catenin contributes to carcinogenesis remain to be disclosed. Here we report isolation of a novel murine gene, Drctnnb1a (down-regulated by Ctnnb1, a), the expression of which was experimentally down-regulated in response to the activated form of beta-catenin. To investigate a possible role of DRCTNNB1A in cancers, we also isolated the human homologue, DRCTNNB1A, the deduced product of which was 91% identical to the murine protein. The transcript was expressed in all human tissues examined, and we assigned the genomic location of DRCTNNB1A to chromosomal band 7p15.3 by in situ hybridization. Expression of DRCTNNB1A in SW480 colon cancer cells was significantly increased in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of the beta-catenin-binding domain of the adenomatous polyposis coli gene into the cells. Furthermore, we documented reduced expression of DRCTNNB1A in 12 of 15 primary colorectal cancers examined, compared with corresponding adjacent noncancerous mucosae. Our results implied that DRCTNNB1A is one of the genes involved in the beta-catenin-Tcf/Lef signaling pathway, and that reduced expression of DRCTNNB1A may have some role in colorectal carcinogenesis.

Animals↗

PubMed2000

Gd(3+)-loaded polyion complex for pH depiction with magnetic resonance imaging.

In clinical diagnosis, gadolinium (Gd) ion/low molecular weight chelater complexes have been used as MRI contrast agents that disperse throughout a particular tissue and cause a brighter appearance in MRI. In order to provide a novel imaging concept for MRI, a contrast agent in which the T(1)-relaxation shortening activity (R(1) relaxivity) changes in response to the pH differences was studied. We prepared a polyion complex (PIC) consisting of a polyanionic Gd-chelater, poly(diethylenetriamine-N,N,N',N", N"-pentaaceto, DTPA) (1,3-propanediamide) (denoted as 1a) loaded with Gd ions at a [Gd]/[DTPA unit] ratio of 0.2 (denoted as 1b), and a polycation, poly[2-(diethylamino)ethyl methacrylate] (denoted as 2). The stoichiometric (based on ionic groups) mixture of 1b and 2 formed complex coacervates from pH 5 to pH 8. The R(1) relaxivity of Gd(3+) in the complex was considerably influenced by the pH, and the relative signal intensity changed from 4 at pH 7.2 to 11 at pH 5.0, as determined by an MRI phantom study. The pH responsivity of the complex solution varied with the composition of the PIC (i.e., the mixing ratio of 1b and 2), allowing us to modulate the pH sensibility. The ionic charge balance and swelling of PIC seemingly were related to the pH-dependent R(1) relaxivity change. It is expected that the PIC-based MRI contrast agent may provide a novel category of MRI methods and be useful in improving the detectability of an MRI-based diagnosis.

Cations↗

PubMed2000

Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress.

Tumor metastasis and invasion were shown to be inhibited by the 2-O-phosphorylated form (Asc2P) of L-ascorbic acid (Asc); intact Asc did not inhibit tumor invasion when added once, but appreciably inhibited it upon repeated addition. The anti-metastatic effect is attributable to a marked enrichment of intracellular Asc by Asc2P, subsequently dephosphorylated. Asc2P scavenged most of the intracellular reactive oxygen species (ROSin), and notably inhibited production of matrix metalloproteases and cell motility. ROSin was decreased by Asc2P more markedly than by Asc added once. Thus, involvement of ROSin in tumor invasion and a potent anti-metastatic therapy by ROSin-decreasing agents are suggested.

Animals↗

PubMed2000

Autoimmune hemolytic anemia (AIHA) in an infant rhesus macaque (Macaca mulatta).

Autoimmune hemolytic anemia (AIHA) is a disorder associated with the destruction of red blood cells (RBCs) by autoantibodies. We report a rare case of AIHA in an infant rhesus macaque (Macaca mulatta) which received a continuous administration of four drugs, a dopamine agonist. dopamine receptor inhibitor, and two gamma-aminobutyric acid receptor inhibitors into the brain during the course of neurophysiological experiments. The main clinical findings were severe anemia and splenomegaly. Hematological and serological examinations revealed the appearance of peripheral erythroblasts and autoantibodies against RBCs. Medical treatments, including washed RBC transfusion and corticosteroids, transiently improved the animal's anemia, but euthanasia was decided on 331 days after the start of the experiment. The pathological findings revealed severe anemia, splenomegaly, and extramedullary hematopoiesis in the liver and kidneys. These findings and the clinical course suggest that this anemia was a warm-antibody type of AIHA induced by the administration of the drugs for the neurophysiological experiment.

Anemia, Hemolytic, Autoimmune↗

PubMed2000

AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1.

The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

Adenomatous Polyposis Coli Protein↗

PubMed2000

Enhanced invasion of Tax-expressing fibroblasts into the basement membrane is repressed by phosphorylated ascorbate with simultaneous decreases in intracellular oxidative stress and NF-kappa B activation.

Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species (ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases (MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin-enriching agents for the prevention against tumor invasion in which ROSin plays a major role.

Animals↗

PubMed2000

Isolation and characterization of human NBL4, a gene involved in the beta-catenin/tcf signaling pathway.

beta-Catenin, a key regulator of cellular proliferation, is often mutated in various types of human cancer. To investigate cellular responses related to the beta-catenin signaling pathway, we applied a differential display method using mouse cells transfected with an activated form of mutant beta-catenin. This analysis and subsequent northern-blot hybridization confirmed that expression of a murine gene encoding NBL4 (novel band 4.1-like protein 4) was up-regulated by activation of beta-catenin. To examine a possible role of NBL4 in cancer, we isolated the human homologue of the murine NBL4 gene by matching mNBL4 against the human EST (expressed sequence tag) database followed by 5' rapid amplification of cDNA ends (5'RACE). The cDNA of hNBL4 encoded a protein of 598 amino acids that shared 87% identity in amino acid sequence with murine NBL4 and 71% with zebrafish NBL4. A 2.2-kb hNBL4 transcript was expressed in all human tissues examined with high levels of expression in brain, liver, thymus and peripheral blood leukocytes and low levels of expression in heart, kidney, testis and colon. We determined its chromosomal localization at 5q22 by fluorescence in situ hybridization. Expression of hNBL4 was significantly reduced when beta-catenin was depleted in SW480 cells, a human cancer cell line that constitutionally accumulates beta-catenin. The results support the view that NBL4 is an important component of the beta-catenin / Tcf pathway and is probably related to determination of cell polarity or proliferation.

Amino Acid Sequence↗