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At least 181 records · Page 10Linked to original sources
PubMed2003

Microarray analysis reveals interleukin-6 as a novel secretory product of the hypothalamo-neurohypophyseal system.

Physiological activation of the hypothalamo-neurohypophyseal system (HNS) by dehydration results is a massive release of vasopressin (VP) from the posterior pituitary. This is accompanied by a functional remodeling of the HNS. In this study we used cDNA arrays in an attempt to identify genes that exhibit differential expression in the hypothalamus following dehydration. Our study revealed nine candidate genes, including interleukin-6 (IL-6) as a putative novel secretory product of HNS worthy of further analysis. In situ hybridization and immunocytochemistry confirmed that IL-6 is robustly expressed in the supraoptic (SON) and the paraventricular (PVN) nuclei of the hypothalamus. By double staining immunofluorescence we showed that IL-6 is largely co-localized with VP in the SON and PVN. In situ hybridization, immunocytochemistry, and Western blotting all revealed IL-6 up-regulation in the SON and PVN following dehydration, thus validating the array data. The same dehydration stimulus resulted in an increase in IL-6 immunoreactivity in the axons of the internal zone of the median eminence and a marked reduction in IL-6-like material in the posterior pituitary gland. We thus suggest that IL-6 takes the same secretory pathway as VP and is secreted from the posterior pituitary following a physiological stimulus.

Animals↗
PubMed2004

Effects of tumor-associated mutations on Rad54 functions.

Yeast RAD54 gene, a member of the RAD52 epistasis group, plays an important role in homologous recombination and DNA double strand break repair. Rad54 belongs to the Snf2/Swi2 protein family, and it possesses a robust DNA-dependent ATPase activity, uses free energy from ATP hydrolysis to supercoil DNA, and cooperates with the Rad51 recombinase in DNA joint formation. There are two RAD54-homologous genes in human cells, hRAD54 and RAD54B. Mutations in these human genes have been found in tumors. These tumor-associated mutations map to conserved regions of the hRad54 and hRad54B proteins. Here we introduced the equivalent mutations into the Saccharomyces cerevisiae RAD54 gene in an effort to examine the functional consequences of these gene changes. One mutant, rad54 G484R, showed sensitivity to DNA-damaging agents and reduced homologous recombination rates, indicating a loss of function. Even though the purified rad54 G484R mutant protein retained the ability to bind DNA and interact with Rad51, it was nearly devoid of ATPase activity and was similarly defective in DNA supercoiling and D-loop formation. Two other mutants, rad54 N616S and rad54 D442Y, were not sensitive to genotoxic agents and behaved like the wild type allele in homologous recombination assays. Consistent with the mild phenotype associated with the rad54 N616S allele, its encoded protein was similar to wild type Rad54 protein in biochemical attributes. Because dysfunctional homologous recombination gives rise to genome instability, our results are consistent with the premise that tumor-associated mutations in hRad54 and Rad54B could contribute to the tumor phenotype or enhance the genome instability seen in tumor cells.

Adenosine Triphosphatases↗
PubMed2003

Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin.

Leptin acts on the brain to regulate body weight and neuroendocrine function. Proopiomelanocortin (POMC) neurons in the hypothalamus are important targets of leptin. These cells express the leptin receptor ObRb, and leptin can regulate POMC mRNA levels, but the cellular mechanisms by which this occurs is unknown. Here we show evidence that leptin stimulates pomc gene transcription via activation of intracellular signal transducer and activator of transcription 3 (STAT3) proteins. In pomc-promoter assays using transfected cells, leptin induces pomc promoter activity. Expression of dominant negative STAT3 strongly suppresses this effect. Furthermore, maximal activation requires the presence of the STAT3-binding site, tyrosine 1138, of ObRb. Mutational analysis identifies a 30-bp promoter element that is required for regulation by leptin. In rats, robust leptin-dependent induction of STAT3 phosphorylation is demonstrated in hypothalamic POMC neurons using double immunohistochemistry. In total, approximately 37% of POMC cells are positive for phospho-STAT3 after leptin treatment. Furthermore, leptin-responsive POMC neurons are concentrated in the rostral region of the hypothalamus. Combined, our data show that a subpopulation of POMC neurons is leptin-responsive and suggest that stimulation of hypothalamic pomc gene expression in these cells requires STAT3 activation. We speculate that STAT3 is critical for leptin-dependent effects on energy homeostasis that are mediated by the central melanocortin system.

Animals↗
PubMed1994

Worldwide collaborative observational study and meta-analysis on allogenic leukocyte immunotherapy for recurrent spontaneous abortion. Recurrent Miscarriage Immunotherapy Trialists Group.

PROBLEM: Recurrent spontaneous abortion (RSA) is a common complication of pregnancy for which there is no known cure. Therefore, effective treatment is needed. Published results from controlled clinical trials of allogeneic leukocyte immunization of women suffering from RSA have given conflicting results. To address this controversy, the international raw data of all patients who had been entered into clinical trials that included a control group were collected and analyzed. The primary question to be answered was whether alloimmune stimulation of the female partner improves the subsequent live birth rate. METHODS: Fifteen clinical centers were identified worldwide because they controlled appropriate raw data. Consequently, nine randomized trials (seven double-blinded) were evaluated independently by two separate data analysis teams to assure conclusions were robust. One team also compared randomized trials to the results of six nonrandomized cohort-controlled studies to test for bias in nonrandomized trials. Factors predicting successful live births among couples with RSA were evaluated by logistic regression. RESULTS: Although the two independent analyses made use of different definitions and utilized different statistical methods, the results of both were similar. The live births ratios (ratio of live births in treatment and control groups) with 95% confidence intervals (CI) were 1.16 (CI, 1.01-1.34, P = 0.031) and 1.21 (CI, 1.04-1.37, P = 0.024), respectively. The absolute differences in live birth rates between treatment and control groups were 8% and 10% in respective analyses. Results in randomized and nonrandomized trials were surprisingly similar despite significant differences in composition of control and treatment groups. Live birth rates were lower with older female partners, more than five abortions, with a positive ANA or with positive anticardiolipin antibodies. Live birth rates were higher if the female partner had prior to treatment serum antibodies to paternal leukocytes or converted from negative to positive with immunization. Approximately 0.5% of controls and 2.1% of treated patients experience side effects for a 1.6% treatment related effect. There was no evidence of an increased risk of adverse effects on the fetus. CONCLUSIONS: Two independent analyses of worldwide data on allogeneic leukocyte immunization for treatment of RSA suggest that alloimmunization may be an effective treatment The treatment effect appears, however, to be small, and the data indicate that immunotherapy helps only 8% to 10% of affected couples. A current lack of diagnostic tests defining patients who most likely would benefit from immunotherapy, precludes the identification of a patient population that would benefit most from such treatment. The efficacy of treatment in such a subgroup could be expected to increase and could be of sufficient magnitude to allow the determination of more effective immunization protocols. This study does not exclude the possibility of a partial correction of a widely prevalent immunology defect by immunotherapy. The presence of such a defect would indicate a need for more effective therapy. The unexplained variation in pregnancy success rates of control groups among centers continues to present a statistical problem, limiting the statistical evaluation of retroactively obtained data.

Abortion, Habitual↗
PubMed2001

Pathogenic effects of D23N Iowa mutant amyloid beta -protein.

Cerebral amyloid beta-protein angiopathy (CAA) is a key pathological feature of patients with Alzheimer's disease and certain related disorders. In these conditions the CAA is characterized by the deposition of Abeta within the cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations have been identified within the Abeta region of the Abeta protein precursor (AbetaPP) gene that appear to enhance the severity of CAA. We recently described a new mutation within the Abeta region (D23N) of AbetaPP that is associated with severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697-705). In the present study, we investigated the effect of this new D23N mutation on the processing of AbetaPP and the pathogenic properties of Abeta. Neither the D23N Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing of AbetaPP expressed in H4 cells. The A21G Flemish mutation, in contrast, resulted in a 2.3-fold increase in secreted Abeta peptide. We also tested synthetic wild-type and mutant Abeta40 peptides for fibrillogenesis and toxicity toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch, D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Abeta40 peptides rapidly assembled in solution to form fibrils, whereas wild-type and A21G Flemish Abeta40 peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N Iowa Abeta40 peptides were found to induce robust pathologic responses in cultured HCSM cells, including elevated levels of cell-associated AbetaPP, proteolytic breakdown of smooth muscle cell alpha-actin, and cell death. Double mutant E22Q,D23N Dutch/Iowa Abeta40 was more potent than either single mutant form of Abeta in causing pathologic responses in HCSM cells. These data suggest that the different CAA mutations in AbetaPP may exert their pathogenic effects through different mechanisms. Whereas the A21G Flemish mutation appears to enhance Abeta production, the E22Q Dutch and D23N Iowa mutations enhance fibrillogenesis and the pathogenicity of Abeta toward HCSM cells.

Amino Acid Sequence↗
PubMed2002

Space-time encoding for high frame rate ultrasound imaging.

Frame rate in ultrasound imaging can be dramatically increased by using sparse synthetic transmit aperture (STA) beamforming techniques. The two main drawbacks of the method are the low signal-to-noise ratio (SNR) and the motion artifacts, that degrade the image quality. In this paper we propose a spatio-temporal encoding for STA imaging based on simultaneous transmission of two quasi-orthogonal tapered linear FM signals. The excitation signals are an up- and a down-chirp with frequency division and a cross-talk of -55 dB. The received signals are first cross-correlated with the appropriate code, then spatially decoded and finally beamformed for each code, yielding two images per emission. The spatial encoding is a Hadamard encoding previously suggested by Chiao et al. [in: Proceedings of the IEEE Ultrasonics Symposium, 1997, p. 1679]. The Hadamard matrix has half the size of the transmit element groups, due to the orthogonality of the temporal encoded wavefronts. Thus, with this method, the frame rate is doubled compared to previous systems. Another advantage is the utilization of temporal codes which are more robust to attenuation. With the proposed technique it is possible to obtain images dynamically focused in both transmit and receive with only two firings. This reduces the problem of motion artifacts. The method has been tested with extensive simulations using Field II. Resolution and SNR are compared with uncoded STA imaging and conventional phased-array imaging. The range resolution remains the same for coded STA imaging with four emissions and is slightly degraded for STA imaging with two emissions due to the -55 dB cross-talk between the signals. The additional proposed temporal encoding adds more than 15 dB on the SNR gain, yielding a SNR at the same order as in phased-array imaging.

Journal Article↗
PubMed2006

Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution.

Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are promising anticancer targets. Here we show that four-repeat human telomeric DNA sequences can adopt two different intramolecular G-quadruplex folds in K+ solution. The two structures contain the (3+1) G-tetrad core, in which three G-tracts are oriented in one direction and the fourth in the opposite direction, with one double-chain-reversal and two edgewise loops, but involve different loop arrangements. This result indicates the robustness of the (3+1) core G-quadruplex topology, thereby suggesting it as an important platform for structure-based drug design. Our data also support the view that multiple human telomeric G-quadruplex conformations coexist in K+ solution. Furthermore, even small changes to flanking sequences can perturb the equilibrium between different coexisting G-quadruplex forms.

DNA↗
PubMed2002

Internal oscillations and instability characteristics of (2+1)-dimensional solitons in a saturable nonlinear medium.

Two related problems on scalar (2+1)-dimensional solitons in a saturable nonlinear medium are investigated. The first one is the internal oscillations of fundamental (single-hump) solitons. Internal modes which cause these oscillations, both with and without angular dependence, are discovered. The visual effect of angle-dependent internal modes on the soliton can be a rotation or spatially uneven breathing of the perturbed soliton. These internal oscillations are very robust and persist for a very long distance. The second problem is the instability of double-hump and radially symmetric solitons. Unstable eigenmodes of these solitons are presented. Contrary to intuition, the instability growth rates decrease to zero when the soliton power becomes high. Thus the instability is strongly suppressed at high powers. This phenomenon is corroborated by our direct numerical simulations.

Journal Article↗
PubMed2006

Two-step phase-shifting interferometry and its application in image encryption.

Conventional phase-shifting interferometry (PSI) needs at least three interferograms. A novel algorithm of two-step PSI, with an arbitrary known phase step, by which a complex object field can be reconstructed with only two interferograms is proposed. This algorithm is then applied to an information security system based on double random-phase encoding in the Fresnel domain. The feasibility of this method and its robustness against occlusion and additional noise attacks are verified by computer simulations. This approach can considerably improve the efficiency of data transmission and is very suitable for Internet use.

Journal Article↗
PubMed1982

Three radioligands compared for determining cytoplasmic estrogen-receptor content of human breast carcinomas.

We compared three radioligands for use in a cytoplasmic estrogen-receptor assay, using pooled cytosol from human breast adenocarcinomas. The estrogen receptor content was determined in vitro by a dextran-coated charcoal method involving a 4-h incubation with and without diethylstilbestrol. Tritiated moxestrol failed to come to equilibrium in 4 h, thereby preventing the use of conventional one-component Scatchard analysis. The use of 125I-labeled estradiol resulted in a higher estimate of estrogen-receptor concentration than that obtained with use of tritiated estradiol. This overestimation was not corrected by Scatchard, double-reciprocal, or Woolf plots, or by two different methods of data analysis: least squared and "robust." An underestimation of the specific activity of iodoestradiol with respect to that of tritiated estradiol and an unrecognized second component of nonreceptor binding could explain this disparity.

Breast Neoplasms↗
PubMed2001

Double molecular imprinting--a new sensor concept for improving selectivity in the detection of polycyclic aromatic hydrocarbons (PAHs) in water.

Highly selective and robust polymer coatings for the detection of polycyclic aromatic hydrocarbons (PAHs) in liquid media have been generated by use of an innovative method of molecular imprinting. By imprinting with two different templates, the selectivity of the polyurethanes used was increased by creating diffusion pathways and molecular cavities. Analyte inclusion was detected both by fluorescence and by use of mass-sensitive transducers. It is possible to optimize layers in respect of the extraction of two different analytes or to achieve extremely high selectivity for a distinct analyte. In this way coatings can be tuned to the lean chrysene, e.g., and it is enriched by a factor of approximately fifty compared with the more quadratic pyrene with the same number of aromatic rings. Measurements of PAHs in water were also performed with a quartz crystal microbalance, which shows that humic acids are not incorporated by the layers and thus do not influence the fluorescence properties of the layers.

Journal Article↗
PubMed2006

Roles of charged residues of rotor and stator in flagellar rotation: comparative study using H+-driven and Na+-driven motors in Escherichia coli.

In Escherichia coli, rotation of the flagellar motor has been shown to depend upon electrostatic interactions between charged residues of the stator protein MotA and the rotor protein FliG. These charged residues are conserved in the Na+-driven polar flagellum of Vibrio alginolyticus, but mutational studies in V. alginolyticus suggested that they are relatively unimportant for motor rotation. The electrostatic interactions detected in E. coli therefore might not be a general feature of flagellar motors, or, alternatively, the V. alginolyticus motor might rely on similar interactions but incorporate additional features that make it more robust against mutation. Here, we have carried out a comparative study of chimeric motors that were resident in E. coli but engineered to use V. alginolyticus stator components, rotor components, or both. Charged residues in the V. alginolyticus rotor and stator proteins were found to be essential for motor rotation when the proteins functioned in the setting of the E. coli motor. Patterns of synergism and suppression in rotor/stator double mutants indicate that the V. alginolyticus proteins interact in essentially the same way as their counterparts in E. coli. The robustness of the rotor-stator interface in V. alginolyticus is in part due to the presence of additional charged residues in PomA but appears mainly due to other factors, because an E. coli motor using both rotor and stator components from V. alginolyticus remained sensitive to mutation. Motor function in V. alginolyticus may be enhanced by the proteins MotX and MotY.

Bacterial Proteins↗
PubMed2005

Improved real-time RT-PCR method for high-throughput measurements using second derivative calculation and double correction.

Quantification of mRNA expression levels using real-time reverse transcription PCR (RT-PCR) is increasingly used to validate results of DNA microarrays or GeneChips. It requires an improved method that is more robust and more suitable for high-throughput measurements. In this report, we compare a user non-influent, second derivative method with that of a user influent, fit point method that is widely used in the literature. We also describe the advantage of using a double correction: one correction using the expression levels of a housekeeping gene of an experiment as an internal standard and a second using reference expression levels of the same housekeeping gene in the tissue or cells. The first correction permits one to decrease errors due to sample preparation and handling, while the second correction permits one to avoid the variation of the results with the variability of housekeeping in each tissue, especially in experiments using various treatments. The data indicate that the real-time PCR method is highly efficient with an efficiency coefficient close to the theoretical value of two. The results also show that the second derivative method is more accurate than the fit point method in quantifying low gene expression levels. Using triplicate experiments, we show that measurement variations using our method are low with a mean of variation coefficients of <1%.

Algorithms↗
PubMed2003

A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder.

BACKGROUND: Homeopathy is commonly used for the treatment of medical and psychological conditions. Such prevalent use, however, is not supported by robust, methodologically sound research. This study evaluates the effect of homeopathic treatment in generalized anxiety disorder, a prevalent mental disorder characterized by an enduring pattern of excessive apprehension and distress and by mental and bodily complaints. METHOD: Forty-four patients with DSM-IV generalized anxiety disorder participated in a randomized, double-blind, placebo-controlled 10-week trial of individually tailored homeopathic remedy. Homeopathic therapy was administered by an expert who followed the traditional routines of homeopathic diagnosis and prescription. Thirty-nine subjects completed the study (20 in the active treatment group and 19 in the placebo group). Subjects' symptoms were rated before treatment and after 5 and 10 weeks of treatment, with the Hamilton Rating Scale for Anxiety (HAM-A) as main outcome measure. Additional measures of outcome included the Brief Symptom Inventory, the Psychological General Well-Being Index, the Hamilton Rating Scale for Depression, the Beck Depression Inventory, Spielberger's State-Trait Anxiety Inventory, and a Visual Analogue Scale of subjective distress. RESULTS: Significant (p <.05) improvement in most measures, including the HAM-A, was observed in both the active treatment and placebo groups, yet no group effect was observed. CONCLUSION: The effect of homeopathic treatment on mental symptoms of patients with generalized anxiety disorder did not differ from that of placebo. The improvement in both conditions was substantial. Improvement of such magnitude may account for the current belief in the efficacy of homeopathy and the current increase in the use of this practice.

Adolescent↗
PubMed1995

Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis.

Indirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solid-phase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain of these double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M:F ratio 55:34), a mean age of 60.4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis.

Adolescent↗
PubMed2006

Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral cortex.

We studied the distribution and cellular localization of Na(+)-coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na(+)-coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na(+)-coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na(+)-coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na(+)-coupled neutral amino acid transporter 2. Na(+)-coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na(+)-coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na(+)-coupled neutral amino acid transporter 1- and Na(+)-coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na(+)-coupled neutral amino acid transporter 1/synaptophysin and Na(+)-coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na(+)-coupled neutral amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate-glutamine cycle. The strong expression of Na(+)-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier suggests that Na(+)-coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.

Amino Acid Transport System A↗
PubMed2005

Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice.

Major pathological findings in Alzheimer's disease (AD) brain include the deposition of amyloid-beta and synapse loss. Synaptic loss has been shown to correlate with the cognitive decline in AD patients, but the relationship between cerebral amyloidosis and synapse loss is complicated by the presence of neurofibrillary tangles and other lesions in AD brain. With the use of the APP23 transgenic mouse model that overexpresses human amyloid precursor protein (APP) with the Swedish double mutation, we investigated whether the development of cortical amyloid deposition was accompanied by synaptic bouton loss. With stereological methods, we show that despite robust age-related cortical amyloid deposition with associated synaptic degeneration, the total number of cortical synaptophysin-positive presynaptic terminals is not changed in 24-month-old animals compared with 3-, 8-, and 15-month-old APP23 mice. Wild-type mice also do not show an age-related loss of presynaptic boutons in the neocortex and are not significantly different from APP23 mice. Synaptophysin Western blotting revealed no significant difference between APP23 mice and wild-type controls at 3 and 25 months of age. Our results suggest that cerebral amyloidosis is not sufficient to account for the global synapse loss in AD. Alternatively, a putative trophic effect of APP may prevent, compensate, or delay a loss of synapses in this mouse model.

Age Factors↗
PubMed2002

Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth.

ErbB-3 (HER3) is a member of the epidermal growth factor receptor family. Increasing evidence suggests that elevated expression of ErbB-3 is important for malignancy. In this study, we found that elevated levels of ErbB-3 expression did not occur in the absence of AP-2gamma in a panel of human mammary epithelial and fibroblasts cell lines. In contrast, there was no association between the expression of AP-2alpha or AP-2beta and the level of ErbB-3, or between AP-2alpha and AP-2gamma double positivity and ErbB-3 expression. In co-transfection experiments, exogenous expression of AP-2gamma robustly activated ErbB-3 promoter activity. Moreover, expression of a dominant negative AP-2 protein, AP-2delta (deleted residues 31-117), not only repressed the ErbB-3 promoter activity but also suppressed endogenous ErbB-3 transcription in the ErbB-3 overexpressing cell line MRC-5VA. Overexpression of AP-2A resulted in a decreased proliferation rate and inhibitin of colony formation. Taken together, these data strongly support a role for the AP-2 gene family, in particular, AP-2gamma, in the control of ErbB-3 expression. Interference with the function of transcription factor AP-2 might provide a potential strategy for modulation of the malignant phenotype.

Breast↗