High Expression of AhR and Environmental Pollution as AhR-Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients with Gastric Cancer-A Pilot Study.

The vast majority of gastric cancer (GC) cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GC, often associated with poor overall survival, has constantly increased in Western countries. Epidemiological studies have reported increased mortality from GC after occupational exposure to pro-carcinogens that are metabolically activated by cytochrome P450 enzymes through aryl hydrocarbon receptor (AhR).

Differential Expression of Genes Involved in Metabolism and Immune Response in Diffuse and Intestinal Gastric Cancers, a Pilot Ptudy.

Gastric cancer (GC) is one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GCs, often associated with poor overall survival, has constantly increased in USA and Europe The molecular basis of diffuse GC aggressivity remains unclear.

Detection of Persistent Organic Pollutants in Omental Adipose Tissue from Patients with Diffuse-Gastric Cancer: A Pilot Study.

The greater omentum represents a specific adipose tissue resected with gastric surgery for cancer. Diffuse gastric adenocarcinoma (diffuse-GC) is of major relevance among gastric cancers due to its unknown origin, aggressiveness, and metastasis in the peritoneal cavity. We postulated that persistent organic pollutants (POPs) could be detected in the greater omentum.

Differential gene expression in growth factors, epithelial mesenchymal transition and chemotaxis in the diffuse type compared with the intestinal type of gastric cancer.

Gastric cancer (GC) is a highly heterogeneous disease and one of the major causes of cancer-related mortality worldwide. Diffuse-type gastric adenocarcinoma (or poorly cohesive- with independent cells) is characterized by aggressive behavior (rapid invasion, chemoresistance and peritoneal metastasis), as compared with intestinal-subtype adenocarcinoma. Diffuse subtype GC additionally has a substantially increasing incidence rate in Europe and the USA, and was often associated with younger age.

Alteration of mammary gland development by bisphenol a and evidence of a mode of action mediated through endocrine disruption.

The development and function of the mammary gland are endocrine-dependent processes, depending on the stage of development. Foetal and/or postnatal exposure to low doses of BPA alters tissue organisation through epithelial proliferation and stroma-epithelial interactions. BPA also alters the expression of E2-dependent epithelial and stroma transcriptomes.

High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism.

Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers.

MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.

Background: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has important roles in angiogenesis. Our knowledge of the significance of VEGF isoforms in human cancer remains incomplete.

Methods: Bioluminescence imaging and transcriptomic analysis were used to study the colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B, respectively) in nude mice.

Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model.

Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats.

Autocrine functions of VEGF in breast tumor cells: adhesion, survival, migration and invasion.

Vascular endothelial growth factor A (VEGF-A) is well known for its key roles in blood vessel growth. Although most studies on VEGF and VEGF receptors have been focused on their functions in angiogenesis and in endothelial cells, the role of VEGF in cancer biology appears as an emerging area of importance. In this context, the presence of VEGF receptors in tumor cells strongly suggests that VEGF-A also promotes a wide range of functions, both in vitro and in vivo, all autocrine functions on tumor cells, including adhesion, survival, migration and invasion.

In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response.

Overexpression of VEGF189 in breast cancer cells induces apoptosis via NRP1 under stress conditions.

The existence of multiple VEGF-A isoforms raised the possibility that they may have distinct functions in tumor growth. We have previously published that VEGF189 and VEGF165 contribute to breast cancer progression and angiogenesis, but VEGF165 induced the most rapid tumor uptake. Since VEGF165 has been described as a survival factor for breast tumor cells, we questioned here the effects of VEGF189 on the survival/apoptosis of MDA-MB-231 cells.

Similar NF-κB gene signatures in TNF-α treated human endothelial cells and breast tumor biopsies.

Background: Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies.

Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis.

Administration of bisphenol A to dams during perinatal period modifies molecular and morphological reproductive parameters of the offspring.

Bisphenol A (BPA) is an estrogenic agonist compound that induces changes in diverse reproductive parameters in rats. The aim of the present study was to determine the effects of BPA given in drinking water containing 10mg/L (approximate dose 1.2mg/kg BW/day), administered chronically to rats during pregnancy and lactation, on reproductive tract parameters of the offspring.

Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism.

Environmental chemicals may affect human health by disrupting endocrine function. Their possible role in the mammary gland and breast tumors is still unknown. Previous studies have demonstrated that vascular endothelial growth factor (VEGF), a key factor in angiogenesis and tumor progression, is an estrogen-regulated gene.

Overexpression of vascular endothelial growth factor 189 in breast cancer cells leads to delayed tumor uptake with dilated intratumoral vessels.

Vascular endothelial growth factor (VEGF) is essential for breast cancer progression and is a relevant target in anti-angiogenesis. Although VEGF121 and VEGF165, the fully or partially secreted isoforms, respectively, have been the focus of intense studies, the role of the cell-associated VEGF189 isoform is not understood. To clarify the contribution of VEGF189 to human mammary carcinogenesis, we established several clones of MDA-MB-231 cells stably overexpressing VEGF189 (V189) and VEGF165 (V165).

Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus.

The induction of vascular endothelial growth factor (VEGF) expression by 17beta-estradiol (E(2)) in many target cells, including epithelial cells, fibroblasts and smooth muscle cells, suggests a role for this hormone in the modulation of angiogenesis and vascular permeability. We have already described a cyclic increase in Flk-1/KDR-expressing capillaries in the human endometrium during the proliferative and mid-secretory phases, strongly suggestive of an E(2) effect on Flk-1/KDR expression in the endometrial capillaries. However, it is unclear whether these processes are due to a direct effect of E(2) on endothelial cells.

VEGF189 stimulates endothelial cells proliferation and migration in vitro and up-regulates the expression of Flk-1/KDR mRNA.

The vascular endothelial growth factor (VEGF) is a critical factor for development of the vascular system in physiological and pathological angiogenesis. This growth factor exists under at least three isoforms, VEGF120/121, VEGF164/165 and VEGF188/189 which are generated by alternative splicing. VEGF isoforms have different affinities for heparan sulphate as well as for VEGF receptors, and may play distinct roles in vascular development.

Paracrine action of vascular endothelial growth factor in the human endometrium: production and target sites, and hormonal regulation.

Vascular endothelial growth factor (VEGF) is an endothelium-specific growth factor with potent angiogenic activity and a stimulator of microvascular permeability. Because endometrial cyclic development is associated with vascular growth, we examined the expression of VEGF protein throughout the menstrual cycle and studied the regulation of VEGF mRNA by ovarian steroids in isolated human endometrial stromal cells. VEGF was localized immunohistochemically in glandular epithelial cells and in the surrounding stroma, as well as in capillaries and spiral arterioles, a localization which has not been described before.

Phytoestrogens as modulators of steroid action in target cells.

Although numerous reports exist on the potential beneficial role of nutritional phytoestrogens in human health, their molecular mechanism in target cells is still not completely understood. Phytoestrogens promote estrogen and antiestrogen effects by interacting with numerous molecules, carrier proteins, enzymes and membrane and nuclear receptors, directly or indirectly involved in the transfer of estrogen signals. The hypothesis that the ER beta subtype plays a key role in antiproliferative effect of phytoestrogens, especially in breast cancer, is examined here.

Transcriptional regulation of vascular endothelial growth factor by estradiol and tamoxifen in breast cancer cells: a complex interplay between estrogen receptors alpha and beta.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic factor for many tumors, including those of endocrine-responsive tissues such as the breast and uterus. Recent studies indicate that 17beta-estradiol (E(2)) modulates VEGF expression in breast and uterine cells, involving transcriptional activation through estrogen receptor (ER) alpha. However, molecular mechanisms of VEGF regulation mediated by the two ER subtypes and the potential role of ERbeta in the control of breast cancer angiogenesis have not yet been investigated.

A dynamic shift of VEGF isoforms with a transient and selective progesterone-induced expression of VEGF189 regulates angiogenesis and vascular permeability in human uterus.

A key mechanism underlying physiological angiogenesis of the human endometrium is its ability to regenerate the vascular capillary network and to perform vascular remodeling (i.e., development of spiral arteries).

Presence of estrogen receptor beta in the human endometrium through the cycle: expression in glandular, stromal, and vascular cells.

The recent discovery of a new isoform of estrogen receptor (ER) beta has prompted the reexamination of estrogen action on target organs. Here, we describe the endometrial expression of human ERbeta and compare its distribution with that of ERalpha in the endometrial functional zone. Using immunocytochemistry with well characterized polyclonal antibodies against ERbeta, we have detected specific ERbeta expression in all endometrial compartments (glandular, stromal, and vascular); the specificity of the immunostaining is confirmed by lack of staining of the uterine sections with anti-ERbeta antibodies previously incubated with peptide preparation.