Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells

Juan, Shu Hui; Lee, Ja Ling; Ho, Pei Yin; Lee, Yi‐Hsuan; Lee, Wen Sen

doi:10.1016/j.ejphar.2005.11.023

Cited by 41 publications

(39 citation statements)

References 22 publications

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“…No staining was observed in the IgG control (see the small inset in each panel in Figure 1). In Western blot analysis, the AhR antibody detected a single band at ?95 kDa in HUVEC and in human placental tissues (Figure 2), corresponding to the human AhR molecular mass reported (Juan et al 2006). The AhR protein levels after normalization with GAPDH or b-actin were similar between N and sPE placentas (Figure 2).…”

Section: Placentasmentioning

confidence: 99%

“…After blocking the nonspecific binding with 1% horse serum albumin for 20 min, one tissue section per slide and one tissue microarray were probed with a rabbit AhR antibody (4 mg/ml and 2 mg/ml for the placental tissues and the human fetal tissue microarray, respectively; Biomol International, Plymouth Meeting, PA) for 1 hr. This antibody has been used to detect human AhR using Western blot analysis and immunohistochemistry (Juan et al 2006). Another tissue section on the same slide and another tissue microarray were probed with preimmune rabbit IgG (Vector Laboratories) at the same concentration as the primary antibody and served as negative controls.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The membranes were first probed with the AhR antibody (1:2000; Biomol International) followed by reprobing with either glyceraldehyde-3-phosphate dehydrogenase (GAPDH; 1:4000; Research Diagnostics, Flanders, NJ) or b-actin (1:5000; Ambion, Austin, TX) antibody as a loading control. Human umbilical vein endothelial cells (HUVEC) isolated from normal-term placentas were used as a positive control for AhR (Juan et al 2006). Proteins were visualized using enhanced chemiluminescence reagents (Amersham Biosciences; Piscataway, NJ), followed by exposure to chemiluminescence films.…”

Section: Western Blot Analysis For Ahr Protein In Placentasmentioning

confidence: 99%

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Expression of Aryl Hydrocarbon Receptor in Human Placentas and Fetal Tissues

Jiang

Wang

Fang

et al. 2010

J Histochem Cytochem.

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The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates many biological processes, including fetal development. In this study, we examined AhR protein expression in human placentas from normal (N) and severe preeclamptic (sPE) pregnancies, as well as human fetal tissues from the second trimester of pregnancy, using immunohistochemistry and/or Western blot analysis. In the placentas, the AhR immuno-reactivity was present primarily in syncytiotrophoblasts. The AhR staining was also seen in endothelium of large blood vessels in villi and endothelium of umbilical cord arteries and veins. No difference in AhR protein levels was found between N and sPE placentas. In fetal tissues, the AhR immunoreactivity was localized in lung, kidney, esophagus, pancreas, liver, testicle, thymus gland, retina, and choroid, mainly in epithelial cells, whereas it was absent in heart, brain, sclera, and thoracic aorta. These findings suggest that the AhR plays a critical role in syncytiotrophoblasts of human placentas and epithelium of many fetal organs. These data also imply that human placentas and those fetal organs with high AhR expression (e.g., lung, kidney, liver, pancreas, and thymus gland) during fetal development are highly susceptible to environmental toxicants such as dioxin.

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Section: Placentasmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Western Blot Analysis For Ahr Protein In Placentasmentioning

confidence: 99%

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Expression of Aryl Hydrocarbon Receptor in Human Placentas and Fetal Tissues

Jiang

Wang

Fang

et al. 2010

J Histochem Cytochem.

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“…The TGF-β pathway, in turn, is controlled by the activity of αv integrins in glioma cells (11). AhR has been described as a regulator of the composition of integrins at the cell surface (13,(20)(21)(22)(23), but inhibitory effects of AhR on FAK phosphorylation, a central mediator of integrin signaling, have also been observed (14,24). These findings provided the rationale for the present study, which aimed at elucidating a possible link between the AhR and integrin signaling pathways in modulating the activity of the TGF-β pathway in glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, certain integrins are overexpressed in tumor cells as well as tumor-associated host cells and may have a profound role in tumor progression (12). AhR in turn may regulate the composition of integrin receptors on the cell surface and signaling of focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase involved in integrin signaling cascades (5,13,14). Here, we aimed at defining a possible interplay of integrins and AhR in the regulation of TGF-β signaling in glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

The aryl hydrocarbon receptor links integrin signaling to the TGF-β pathway

et al. 2015

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Glioblastoma is the most common and aggressive form of intrinsic brain tumor. Transforming growth factor (TGF)-represents a central mediator of the malignant phenotype of these tumors by promoting invasiveness and angiogenesis, maintaining tumor cell stemness and inducing profound immunosuppression. Integrins, which are highly expressed in glioma cells, interact with the TGF-pathway. Furthermore, a link has been described between activity of the transcription factor aryl hydrocarbon receptor (AhR) and TGF-expression. Here we demonstrate that integrin inhibition, using v, 3 or 5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity. These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a post-transcriptional level. AhR-null astrocytes, AhR-null hepatocytes or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-signaling, indicating that AhR mediates integrin control of the TGF-pathway. Accordingly, there was a significant correlation of v integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo. In summary, this study identifies a signaling network comprising integrins, AhR and TGF-and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR-and TGF--controlled features of malignancy in human glioblastoma. Here we demonstrate that integrin inhibition, using αv, β3 or β5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity.These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a posttranscriptional level. AhR-null astrocytes, AhR-null hepatocytes, or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-β signaling indicating that AhR mediates integrin control of the TGF-β pathway. Accordingly, there was a significant correlation of αv integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo.In summary, this study identifies a signaling network comprising integrins, AhR and TGF-β and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR-and TGF--controlled features of malignancy in human glio...

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Role of AHR in the Development of the Liver and Blood Vessels

Ichihara

2011

The AH Receptor in Biology and Toxicology

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Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells

Cited by 41 publications

References 22 publications

Expression of Aryl Hydrocarbon Receptor in Human Placentas and Fetal Tissues

Expression of Aryl Hydrocarbon Receptor in Human Placentas and Fetal Tissues

The aryl hydrocarbon receptor links integrin signaling to the TGF-β pathway

Role of AHR in the Development of the Liver and Blood Vessels

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