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Biomedical subjects

D H Nguyen

Publications and source records attributed to D H Nguyen.

At least 19 recordsLinked to original sources
PubMed2006

Practical management of avian influenza in humans.

There has been much alarm about avian influenza and its potential for a global pandemic ever since the current epidemic of avian influenza infections in humans began in 2003. While there have been a number of published reports on the clinical features of avian influenza, there are few guidelines on the practical management of patients with avian influenza. A symposium organised by the Society of Infectious Disease (Singapore), Society of Intensive Care Medicine and the Singapore General Hospital was held in Singapore to gather the views of experts from Turkey, Thailand, Vietnam and Indonesia who collectively had first-hand experience of the management of the majority (more than 100 of 192) of cases of avian influenza worldwide. The experts emphasised the importance of adapting international guidelines to the practicalities of situations on the ground. There was stress on wide screening using clinical criteria primarily, molecular diagnostic techniques (with reference laboratory confirmation) for diagnosis, and rational use of antiviral prophylaxis as well as infection control using at least surgical masks, gowns and gloves. A detailed analysis of data from a pooled database from these and other affected countries is critical to building up the evidence base for practical internationally applicable guidelines.

Antiviral Agents↗
PubMed2004

Lack of effect of 10 kV/m 60 Hz electric field exposure on pregnant dairy heifer hormones.

Sixteen pregnant Holstein heifers weighing 521 +/- 46 kg, at 3.3 +/- 0.7 months of gestation and 2.2 +/- 2.0 months of age were confined to wooden metabolism cages and were exposed to a vertical electric field (EF) of 10.0 +/- 0.4 kV/m and an artificial light cycle of 12 h light-12 h dark. The heifers were divided into two replicates of eight each. Each replicate was divided into two groups of four animals each, one group becoming the non-exposed and the second, the EF exposed group. The exposed group were housed in metabolism cages in an area where EF were generated, and the non-exposed group, in metabolism cages located in the adjacent area where the EF was less than 2% of that present in the exposed area. The test animals were subject to the different treatments for 4 weeks continuously. After 4 weeks, the animals switched treatment, the exposed group becoming the non-exposed group and vice-versa. Then the treatment continued for 4 more weeks. Catheters were inserted into the jugular vein of the animals, and blood samples were collected on twice a week to estimate the serum concentration of progesterone (P4), melatonin (MLT), prolactin (PRL), and insulin-like growth factor-1 (IGF-1). Feed consumption was measured daily and feed samples were collected twice a week. The results indicated that exposure of dairy cattle to EF similar to those encountered directly underneath a 735 kV high tension electrical power line carrying a maximum load of current, cannot be associated with any variation in the experimental variables mentioned above. An exception to this, is the variation in MLT, which was associated with the EF exposure. Due to the inconsistency of the MLT response in the different replicates, caution should be exercised in the interpretation of this phenomenon.

Animals↗
PubMed2004

Blood melatonin and prolactin concentrations in dairy cows exposed to 60 Hz electric and magnetic fields during 8 h photoperiods.

Two experiments were conducted to test the hypothesis that electric and magnetic field (EMF) exposure may result in endocrine responses similar to those observed in animals exposed to long days. In the first experiment, 16 lactating, pregnant Holstein cows were assigned to two replicates according to a crossover design with treatment switchback. All animals were confined to wooden metabolic cages and maintained under short day photoperiods (8 h light/16 h dark). Treated animals were exposed to a vertical electric field of 10 kV/m and a horizontal magnetic field of 30 microT (EMF) for 16 h/day for 4 weeks. In a second, similar experiment, 16 nonlactating, nonpregnant Holstein cows subjected to short days were exposed to EMF, using a similar protocol, for periods corresponding to the duration of one estrous cycle. In the first experiment, circulating MLT concentrations during the light period showed a small numerical decrease during EMF exposure (P < .05). Least-square means for the 8 h light period were 9.9 versus 12.4 pg/ml, SE = 1.3. Melatonin concentrations during the dark period were not affected by the treatment. A similar trend was observed in the second experiment, where MLT concentrations during the light period tended to be lower (8.8 pg/ml vs. 16.3 pg/ml, P < .06) in the EMF exposed group, and no effects were observed during the dark period. Plasma prolactin (PRL) was increased in the EMF exposed group (16.6 vs. 12.7 ng/ml, P < .02) in the first experiment. In the second experiment, the overall PRL concentrations found were lower, and the mean plasma PRL concentration was not affected by treatment. These experiments provide evidence that EMF exposure may modify the response of dairy cows to photoperiod.

Animals↗
PubMed2003

Responses of the estrous cycle in dairy cows exposed to electric and magnetic fields (60 Hz) during 8-h photoperiods.

To study the effects of exposure to extremely low frequency (ELF) electric and magnetic fields (EMF) on the estrous cycle of dairy cows under short-day photoperiod, 16 non-lactating, non-pregnant Holstein cows were exposed to a vertical electric field of 10 kV/m and a horizontal magnetic field of 30 microT for 16 h per day in a cross-over design consisting of two sequences. Each sequence included three periods, and each period corresponded to the duration of one estrous cycle. All animals were maintained under short photoperiod (8 h light/16 h dark) during the trial. Exposure to EMF had an impact on the duration of a complete estrous cycle (P<0.01) and on the duration of the luteal phase (P<0.01). The mean duration of one cycle was 19.5+/-0.4 for the control and 21.3+/-0.4 days for the exposed animals, respectively. The mean duration of the luteal phase was 15.4+/-0.4 days for the control and 17.2+/-0.4 days for the exposed group. The total area under the progesterone (P(4)) curve, the amplitude of the curve or the slope of the P(4) rise at the onset of the luteal phase were not affected by EMF exposure. Results indicate that exposure to EMF may increase the duration of the estrous cycle.

Animals↗
PubMed2003

Effect of 10 kV, 30 microT, 60 Hz electric and magnetic fields on milk production and feed intake in nonpregnant dairy cattle.

Milk production is the main agricultural income in the province of Québec, and the electrical distribution network traverses the rural dairy production region. This study evaluates the hypothesis that electric and magnetic fields may affect dairy production. Sixteen multiparous nonpregnant lactating Holstein cows (weighing 662 +/- 65 kg and with 150.4 +/- 40 days of lactation) were confined to wooden metabolic crates during the experiment with a 12:12 h light:dark cycle. The cows were divided into two replicates of eight cows each and exposed to a vertical EF of 10 kV/m and an uniform horizontal MF of 30 microT at 60 Hz. Replicate one was exposed for three periods. Each period was represented by an estrous cycle ranging from 24 to 27 days. During the first period, the electric and magnetic fields (E&MF) were off; during the second period they were on; and during the final period, they were off. The second replicate was exposed for three periods also, but the exposure protocol was reversed (first period, on; second period, off; last period, on). Exposure to E&MF (on) resulted in an average decrease of 4.97, 13.78, and 16.39% in milk yield, fat corrected milk yield, and milk fat, respectively; and an increase of 4.75% in dry matter intake.

Animals↗
PubMed2002

Accumulation of PN1 and PN3 sodium channels in painful human neuroma-evidence from immunocytochemistry.

BACKGROUND: The axolemmal distribution and density of voltage-gated sodium channels largely determines the electrical excitability of sprouting neurites. Recent evidence suggests that accumulation of sodium channels at injured axonal tips may be responsible for ectopic axonal hyperexcitability and the resulting abnormal sensory phenomena of pain and paresthesias. For future improvement in pain management it is necessary to identify structurally significant generators of autorhythmicity. A first step in this regard will be to determine the predominant types of sodium channels in injured axons. The opportunity to test human specimens from painful and non-painful neuroma is of great value. METHODS: We employed immunocytochemical methods to investigate if two types of highly specific voltage-gated sodium channel subtypes could be detected in sections of human neuroma. FINDINGS: Both subtypes of sodium channels PN1 and PN3 accumulated abnormally in human neuromas. The immunoreactive pattern was more pronounced in painful neuromas. This is in contrast to previous reports that focused either on PN1 or PN3 as main generators of hyperexcitability induced pain. INTERPRETATION: Both, PN1 and PN3 seem to be involved in hyperexcitability induced pain. It can be expected that a variety of other highly specific voltage gated sodium channel subtypes will be detected in regenerating peripheral nerve in the near future, which contribute to the development of neuropathic pain states. Thus, in order to therapeutically control hyperexcitability induced neuropathic pain, it might be worthwhile to develop pharmaceuticals that can selectively block different sodium channel subtypes and subunits.A review of the role of sodium channels in neuropathic pain is implemented in the discussion.

Humans↗
PubMed2002

Solid-phase synthesis of DNA binding polyamides on oxime resin.

Control of the energetics and specificity of DNA binding polyamides is necessary for inhibition of protein-DNA complex formation and gene regulation studies. Typically, solid-phase methods using Boc monomers for synthesis have depended on Boc-beta-Ala-PAM resin which affords a beta-alanine-Dp tail at the C-terminus, after cleavage with N,N-dimethylaminopropylamine (Dp). To address the energetic consequences of this tail for DNA minor groove binding, we describe an alternative solid phase method employing the Kaiser oxime resin which allows the synthesis of polyamides with incrementally shortened C-terminal tails. Polyamides without Dp and having methyl amide tails rather than beta-alanine show similar affinity relative to the standard beta-Dp tail. The truncated tail diminishes the A,T base pair energetic preference of the beta-Dp tail which will allow a greater variety of DNA sequences to be targeted by hairpin polyamides.

Combinatorial Chemistry Techniques↗
PubMed2002

Effect of electric and magnetic fields (60 Hz) on production, and levels of growth hormone and insulin-like growth factor 1, in lactating, pregnant cows subjected to short days.

Electric and magnetic fields (EMF) are generated by the transmission of electricity through high tension lines traversing rural areas. Previous studies showed increased dry matter intake (DMI) and fat corrected milk in dairy cows exposed to EMF. Because EMF exposure has been shown to suppress pineal release of melatonin in some species, it was hypothesized that EMF effects resemble those of exposure to long days. Previous studies have shown that DMI and milk production increase in dairy cattle in response to long day photoperiods, and this has been observed in association with increased circulating insulin-like growth factor 1 (IGF-1), but not growth hormone (GH). The hypothesis that EMF act by modifying the response to photoperiod was tested by subjecting dairy cows to controlled EMF exposure while keeping them under short-day conditions. Sixteen lactating, pregnant Holstein cows were exposed to a vertical electric field of 10 kV/m and a horizontal magnetic field of 30 microT in a crossover design with treatment switchback. Two groups of eight cows each were exposed to EMF for 16 h/d in either oftwo sequences. Each sequence consisted of three consecutive 28-d periods. All animals were maintained under short day conditions (8 h light, 16 h dark) during the trial. DMI and plasma IGF-1 were increased (P < 0.01) during EMF exposure (17.03 vs.16.04 kg/d, SE = 0.4; 137 +/- 6 ng/ml vs 126 +/- 6, respectively). The mean GH concentration was not affected, but a treatment x hour interaction was detected, with GH lower for the EMF exposed animals during the first 16 h of the sampling period, and higher for the last 8 h. Overall, the yield of milk or its components was not affected by EMF exposure, but milk yield was significantly higher for the exposed animals during wk 4 of treatment.

Animals↗
PubMed2001

Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1.

In a previous study we showed that budding of HIV-1 particles occurs at highly specialized membrane microdomains known as lipid rafts. These microdomains are characterized by a distinct lipid composition that includes high concentrations of cholesterol, sphingolipids, and glycolipids. Since cholesterol is known to play a key role in the entry of some other viruses, our observation of HIV budding from lipid rafts led us to investigate the role in HIV-1 entry of cholesterol and lipid rafts in the plasma membrane of susceptible cells. We have used 2-OH-propyl-beta-cyclodextrin (beta-cyclodextrin) to deplete cellular cholesterol and disperse lipid rafts. Our results show that removal of cellular cholesterol rendered primary cells and cell lines highly resistant to HIV-1-mediated syncytium formation and to infection by both CXCR4- and CCR5-specific viruses. beta-Cyclodextrin treatment of cells partially reduced HIV-1 binding, while rendering chemokine receptors highly sensitive to antibody-mediated internalization. There was no effect on CD4 expression. All of the above-described effects were readily reversed by incubating cholesterol-depleted cells with low concentrations of cholesterol-loaded beta-cyclodextrin to restore cholesterol levels. Cholesterol depletion made cells resistant to SDF-1-induced binding to ICAM-1 through LFA-1. Since LFA-1 contributes significantly to cell binding by HIV-1, this latter effect may have contributed to the observed reduction in HIV-1 binding to cells after treatment with beta-cyclodextrin. Our results indicate that cholesterol may be critical to the HIV-1 coreceptor function of chemokine receptors and is required for infection of cells by HIV-1.

Cell Line↗
PubMed2001

The clinical utility of multimarker RT-PCR in the detection of occult metastasis in patients with melanoma.

Cutaneous melanoma is characterized by a high propensity for metastasis. Currently, surgical intervention remains the mainstay of therapy. This approach has proven most beneficial when the diagnosis is of early stage primary lesions. Likewise, patients undergoing resection for a solitary site of metastasis have shown a survival advantage. Identification of metastatic disease depends predominantly on radiographic techniques requiring the presence of significant tumor burdens for successful imaging. However, at that time, the role of surgery and/or biochemotherapy may be of limited value. Techniques to identify minimal disease states may permit more accurate assessment of prognosis. The detection of occult tumor cells by RT-PCR in the blood, lymph nodes, and bone marrow of melanoma patients provides one such approach to monitor tumor progression. Single-marker RT-PCR has been used as one such approach but is noted to have limitations in sensitivity and specificity based on the heterogeneity of tumor marker expression among tumors as well as within an individual tumor lesion or among multiple lesions in individual patients. We employed a multimarker reverse transcriptase polymerase chain reaction assay that demonstrates improved sensitivity over a single-marker approach. Currently, the consequences of detecting systemic subclinical metastasis remain unknown pending longer-term follow-up. The detection of occult melanoma cells using molecular techniques in conjunction with known clinicopathologic prognostic factors may provided a novel and efficient approach in monitoring tumor progression and further identify high-risk patients diagnosed early in the disease course.

Biomarkers, Tumor↗
PubMed2001

Alternative heterocycles for DNA recognition: an N-methylpyrazole/N-methylpyrrole pair specifies for A.T/T.A base pairs.

Side-by-side pairs of three five-membered rings, N-methylpyrrole (Py), N-methylimidazole (Im), and N-methylhydroxy-pyrrole (Hp), have been demonstrated to distinguish each of the four Watson Crick base pairs in the minor groove of DNA. However, not all DNA sequences targeted by these pairing rules achieve affinities and specificities comparable to DNA binding proteins. We have initiated a search for new heterocycles which can expand the sequence repetoire currently available. Two heterocyclic aromatic amino acids. N-methylpyrazole (Pz) and 4-methylthiazole (Th), were incorporated into a single position of an eight-ring polyamide of sequence ImImXPy-gamma-lmPyPyPy-beta-Dp to examine the modulation of affinity and specificity for DNA binding by a Pz/Py pair and or a Th/Py pair. The X/Py pairings Pz/Py and Th/Py were evaluated by quantitative DNase I footprint titrations on a DNA fragment with the four sites 5'-TGGNCA-3' (N=T, A, G, C). The Pz/Py pair binds T.A and A.T with similar affinity to a Py/Py pair but with improved specificity. disfavoring both G.C and C.G by about 100-fold. The Th/Py pair binds poorly to all four Watson Crick base pairs. These results demonstrate that in some instances new heterocyclic aromatic amino acid pairs can be incorporated into imidazole-pyrrole polyamides to mimic the DNA specificity of Py/Py pairs which may be relevant as biological criteria in animal studies become important.

Base Pairing↗
PubMed2001

Towards a minimal motif for artificial transcriptional activators.

BACKGROUND: Most transcriptional activators minimally comprise two functional modules, one for DNA binding and the other for activation. Several activators also bear an oligomerization region and bind DNA as dimers or higher order oligomers. In a previous study we substituted these domains of a protein activator with synthetic counterparts [Mapp et al., Proc. Natl. Acad. Sci. USA 97 (2000) 3930-3935]. An artificial transcriptional activator, 4.2 kDa in size, comprised of a DNA binding hairpin polyamide tethered to a 20 residue activating peptide (AH) was shown to stimulate promoter specific transcription [Mapp et al., Proc. Natl. Acad. Sci. USA 97 (2000) 3930-3935]. The question arises as to the general nature and the versatility of this minimal activator motif and whether smaller ligands can be designed which maintain potent activation function. RESULTS: Here we have replaced the 20 amino acid AH peptide with eight or 16 residues derived from the activation domain of the potent viral activator VP16. The 16 residue activation module coupled to the polyamide activated transcription over two-fold better than the analogous AH conjugate. Altering the site of attachment of the activation module on the polyamide allowed reduction of the intervening linker from 36 atoms to eight without significant diminution of the activation potential. In this study we also exchanged the polyamide to target a different sequence without compromising the activation function further demonstrating the generality of this design. CONCLUSIONS: The polyamide activator conjugates described here represent a class of DNA binding ligands which are tethered to a second functional moiety, viz. an activation domain, that recruits elements of the endogenous transcriptional machinery. Our results define the minimal structural elements required to construct artificial, small molecule activators. If such activators are cell-permeable and can be targeted to designated sites in the genome, this series of conjugates may then serve as a tool to study mechanistic aspects of transcriptional regulation and eventually to modulate gene expression relevant to human diseases.

Base Sequence↗
PubMed2001

A meta-analytic review of gender differences in perceptions of sexual harassment.

Research on gender differences in perceptions of sexual harassment informs an ongoing legal debate regarding the use of a reasonable person standard instead of a reasonable woman standard to evaluate sexual harassment claims. The authors report a meta-analysis of 62 studies of gender differences in harassment perceptions. An earlier quantitative review combined all types of social-sexual behaviors for a single meta-analysis; the purpose of this study was to investigate whether the magnitude of the female-male difference varies by type of behavior. An overall standardized mean difference of 0.30 was found, suggesting that women perceive a broader range of social-sexual behaviors as harassing. However, the meta-analysis also found that the female-male difference was larger for behaviors that involve hostile work environment harassment, derogatory attitudes toward women, dating pressure, or physical sexual contact than sexual propositions or sexual coercion.

Adult↗
PubMed2000

Urokinase-type plasminogen activator stimulates the Ras/Extracellular signal-regulated kinase (ERK) signaling pathway and MCF-7 cell migration by a mechanism that requires focal adhesion kinase, Src, and Shc. Rapid dissociation of GRB2/Sps-Shc complex is associated with the transient phosphorylation of ERK in urokinase-treated cells.

Urokinase-type plasminogen activator (uPA) stimulates MCF-7 cell migration by binding to the UPA receptor and activating the Ras-extracellular signal-regulated kinase (Ras-ERK) signaling pathway. Studies presented here show that soluble uPA receptor and a peptide derived from the linker region between domains 1 and 2 of the uPA receptor also stimulate cellular migration via a mitogen-activated protein kinase/ERK kinase (MEK)-dependent pathway. Signaling proteins that function upstream of Ras in uPA- stimulated cells remain undefined. To address this problem, we transfected MCF-7 cells to express the noncatalytic carboxylterminal domain of focal adhesion kinase (FAK), FAK(Y397F), kinase-defective c-Src, or Shc FFF, all of which express dominant-negative activity. In each case, ERK phosphorylation and cellular migration in response to uPA were blocked. Both activities were rescued by co-transfecting the cells to express constitutively active MEK1, indicating that FAK, c-Src, and Shc are upstream of MEK. Shc was tyrosine-phosphorylated in uPA-treated cells. The level of phosphorylated Shc was increased within 1 min and remained increased for at least 30 min. Sos co-immunoprecipitated with Shc in cells that were treated with uPA for 1-2.5 min, probably reflecting the formation of Shc-Grb2/Sos complex; however, by 10 min, co-immunoprecipitation of Sos with Shc was no longer observed. Rapid dissociation of Sos from Shc represents a possible mechanism for the transient phosphorylation of ERK in uPA-treated MCF-7 cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts.

A number of recent studies have demonstrated the significance of detergent-insoluble, glycolipid-enriched membrane domains or lipid rafts, especially in regard to activation and signaling in T lymphocytes. These domains can be viewed as floating rafts composed of sphingolipids and cholesterol which sequester glycosylphosphatidylinositol (GPI)-linked proteins, such as Thy-1 and CD59. CD45, a 200-kDa transmembrane phosphatase protein, is excluded from these domains. We have found that human immunodeficiency virus type 1 (HIV-1) particles produced by infected T-cell lines acquire the GPI-linked proteins Thy-1 and CD59, as well as the ganglioside GM1, which is known to partition preferentially into lipid rafts. In contrast, despite its high expression on the cell surface, CD45 was poorly incorporated into virus particles. Confocal fluorescence microscopy revealed that HIV-1 proteins colocalized with Thy-1, CD59, GM1, and a lipid raft-specific fluorescent lipid, DiIC(16)(3), in uropods of infected Jurkat cells. CD45 did not colocalize with HIV-1 proteins and was excluded from uropods. Dot immunoassay of Triton X-100-extracted membrane fractions revealed that HIV-1 p17 matrix protein and gp41 were present in the detergent-resistant fractions and that [(3)H]myristic acid-labeled HIV Gag showed a nine-to-one enrichment in lipid rafts. We propose a model for the budding of HIV virions through lipid rafts whereby host cell cholesterol, sphingolipids, and GPI-linked proteins within these domains are incorporated into the viral envelope, perhaps as a result of preferential sorting of HIV Gag to lipid rafts.

Glycolipids↗
PubMed2000

Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion.

The low density lipoprotein receptor-related protein (LRP) has been reported to regulate cellular migration. In this study, an antisense RNA expression strategy was used to reduce LRP to undetectable levels in HT 1080 fibrosarcoma cells. The LRP-deficient cells demonstrated increased levels of cell-surface uPAR, higher levels of uPA in conditioned medium, increased migration on vitronectin-coated surfaces, and increased invasion of Matrigel. LRP-deficient cells also demonstrated increased levels of phosphorylated extracellular signal-regulated kinase (ERK) in the absence of exogenous stimulants. Antibodies which block binding of endogenously produced uPA to uPAR reduced ERK phosphorylation and migration of LRP-deficient cells to the levels observed with control cells. Inhibitors of ERK activation, including PD098059 and dominant-negative MEK1, also decreased the migration of LRP-deficient but not control cells. By contrast, constitutively active MEK1 stimulated the migration of control but not LRP-deficient cells. Although Matrigel invasion by LRP-deficient cells was inhibited by the proteinase inhibitor, aprotinin, PD098059 in combination with aprotinin was necessary for an optimal effect. Expression of the VLDL receptor in LRP-deficient cells reversed the changes in cellular migration and invasion. These studies demonstrate that binding of endogenously produced uPA to uPAR may serve as a major determinant of basal levels of activated ERK and, by this mechanism, regulate cellular migration and invasion. By regulating the uPA/uPAR system, LRP may also regulate ERK activation, cellular migration, and invasion.

Aprotinin↗
PubMed1999

Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner.

Urokinase-type plasminogen activator (uPA) activates the mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) 1 and 2, in diverse cell types. In this study, we demonstrate that uPA stimulates migration of MCF-7 breast cancer cells, HT 1080 fibrosarcoma cells, and uPAR-overexpressing MCF-7 cells by a mechanism that depends on uPA receptor (uPAR)-ligation and ERK activation. Ras and MAP kinase kinase (MEK) were necessary and sufficient for uPA-induced ERK activation and stimulation of cellular migration, as demonstrated in experiments with dominant-negative and constitutively active mutants of these signaling proteins. Myosin light chain kinase (MLCK) was also required for uPA-stimulated cellular migration, as determined in experiments with three separate MLCK inhibitors. When MCF-7 cells were treated with uPA, MLCK was phosphorylated by a MEK-dependent pathway and apparently activated, since serine-phosphorylation of myosin II regulatory light chain (RLC) was also increased. Despite the transient nature of ERK phosphorylation, MLCK remained phosphorylated for at least 6 h. The uPA-induced increase in MCF-7 cell migration was observed selectively on vitronectin-coated surfaces and was mediated by a beta1-integrin (probably alphaVbeta1) and alphaVbeta5. When MCF-7 cells were transfected to express alphaVbeta3 and treated with uPA, ERK was still phosphorylated; however, the cells did not demonstrate increased migration. Neutralizing the function of alphaVbeta3, with blocking antibody, restored the ability of uPA to promote cellular migration. Thus, we have demonstrated that uPA promotes cellular migration, in an integrin-selective manner, by initiating a uPAR-dependent signaling cascade in which Ras, MEK, ERK, and MLCK serve as essential downstream effectors.

Antibodies↗