Expression of dual angiogenic/neurogenic growth factors in human primary brain tumors

Brain tumors, benign or malignant, are characterized by a very high degree of vascularization. Recent accumulating evidence suggests that during development the neuronal wiring follows the same routes as the vasculature and that these two systems may share some of the same factors for guidance. Thus, expression of dual angiogenic/neurogenic growth factors was evaluated by insitu hybridization in human primary brain tumors of three different types, i.e., astrocytomas, oligodendrogliomas, and ependymomas, of increasing grades, in relation with the grade and type of the tumor. For this evaluation we selected vascular endothelial growth factor (VEGF-A) and its receptors VEGF-R1 and VEGF-R2 and the neuropilins1 and 2 (NRP-1 and NRP-2), which have proangiogenic properties, platelet-derived growth factor (PDGF) receptor-beta (PDGF-Rβ), which is required for the functional maturation of blood vessels, the ephrins and their Eph receptors, angiotensinogen (AGT) and thrombospondin-2 (TSP-2), which have potential antiangiogenic properties, and netrin-1 (Net-1), which regulates vascular architecture. We show that the expression of the VEGF-NRP system, PDGF-Rβ, TSP-2, AGT, and Net-1 are differentially regulated, either increased or decreased, in relation with the type and grade of the tumor, whereas regulation of the ephrinB system does not seem to be relevant in these human brain tumor

Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans

Specific germline activating point mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) result in autosomal dominant human skeletal dysplasias. The identification in multiple myeloma and in two epithelial cancers—bladder and cervical carcinomas—of somatic FGFR3 mutations identical to the germinal activating mutations found in skeletal dysplasias, together with functional studies, have suggested an oncogenic role for this receptor. Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated. Here, we targeted an activated receptor mutant (S249C FGFR3) to the basal cells of the epidermis of transgenic mice. Mice expressing the transgene developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. We therefore screened a series of 62 cases of seborrheic keratosis for FGFR3 mutations. A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. Our findings directly implicate FGFR3 activation as a major cause of benign epidermal tumors in human

Transglutaminase 2 et Lysyl oxidase liKe 2 (deux enzymes de remodelage de la matrice extracellulaire endothéliale régulée par l'hypoxie et impliquées dans l'angiogenèse)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Expression au cours de l'ontogenèse et rôle du système rénine-angiotensine dans l'hématopoïèse primitive

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Biologie des stades larvaires d'Euthycera cribrata (Rondani 1868), parasitoïde de Gastéropodes terrestres. Premier cycle expérimental d'une espèce du genre Euthycera Latreille 1829 [Dipt. Sciomyzidae]

Vala Jean-Claude, Reidenbach Jean-Marie, Gasc Charles. Biologie des stades larvaires d'Euthycera cribrata (Rondani 1868), parasitoïde de Gastéropodes terrestres. Premier cycle expérimental d'une espèce du genre Euthycera Latreille 1829 [Dipt. Sciomyzidae]. In: Bulletin de la Société entomologique de France, volume 88 (3-4), Mars-avril 1983. Livre du Cent Cinquantenaire. Premier congrès international des entomologistes d'expression française. Paris, 6-9 juillet 1982. Comptes rendus des travaux. II. pp. 250-258

Biologie des stades larvaires d'Euthycera cribrata (Rondani 1868), parasitoïde de Gastéropodes terrestres. Premier cycle expérimental d'une espèce du genre Euthycera Latreille 1829 [Dipt. Sciomyzidae]

Vala Jean-Claude, Reidenbach Jean-Marie, Gasc Charles. Biologie des stades larvaires d'Euthycera cribrata (Rondani 1868), parasitoïde de Gastéropodes terrestres. Premier cycle expérimental d'une espèce du genre Euthycera Latreille 1829 [Dipt. Sciomyzidae]. In: Bulletin de la Société entomologique de France, volume 88 (3-4), Mars-avril 1983. Livre du Cent Cinquantenaire. Premier congrès international des entomologistes d'expression française. Paris, 6-9 juillet 1982. Comptes rendus des travaux. II. pp. 250-258

A chicken model of pharmacologically-induced Hirschsprung disease reveals an unexpected role of glucocorticoids in enteric aganglionosis

International audienceThe enteric nervous system originates from neural crest cells that migrate in chains as they colonize the embryonic gut, eventually forming the myenteric and submucosal plexus. Failure of the neural crest cells to colonize the gut leads to aganglionosis in the terminal gut, a pathological condition called Hirschsprung disease (HSCR) in humans, also known as congenital megacolon or intestinal aganglionosis. One of the characteristics of the human HSCR is its variable penetrance, which may be attributable to the interaction between genetic factors, such as the endothelin-3/endothelin receptor B pathway, and non-genetic modulators, although the role of the latter has not well been established. We have created a novel HSCR model in the chick embryo allowing to test the ability of non-genetic modifiers to alter the HSCR phenotype. Chick embryos treated by phosphoramidon, which blocks the generation of endothelin-3, failed to develop enteric ganglia in the very distal bowel, characteristic of an HSCR-like phenotype. Administration of dexamethasone influenced the phenotype, suggesting that glucocorticoids may be environmental modulators of the penetrance of the aganglionosis in HSCR disease

Multiple Promoters in the WNK1 Gene: One Controls Expression of a Kidney-Specific Kinase-Defective Isoform

WNK1 is a serine-threonine kinase, the expression of which is affected in pseudohypoaldosteronism type II, a Mendelian form of arterial hypertension. We characterized human WNK1 transcripts to determine the molecular mechanisms governing WNK1 expression. We report the presence of two promoters generating two WNK1 isoforms with a complete kinase domain. Further variations are achieved by the use of two polyadenylation sites and tissue-specific splicing. We also determined the structure of a kidney-specific isoform regulated by a third promoter and starting at a novel exon. This transcript is kinase defective and has a predominant expression in the kidney compared to the other WNK1 isoforms, with, furthermore, a highly restricted expression profile in the distal convoluted tubule. We confirmed that the ubiquitous and kidney-specific promoters are functional in several cells lines and identified core promoters and regulatory elements. In particular, a strong enhancer element upstream from the kidney-specific exon seems specific to renal epithelial cells. Thus, control of human WNK1 gene expression of kinase-active or -deficient isoforms is mediated predominantly through the use of multiple transcription initiation sites and tissue-specific regulatory elements