The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

BACKGROUND: The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression

Effets de la fréquence du voisinage orthographique interlangue lors de la reconnaissance visuelle de mots chez les bilingues

Summary : Interlingual neighborhood frequency effects in bilingual visual word recognition Interlingual orthographic neighborhood frequency was manipulated in a monolingual lexical decision task and a language decision task. The material was composed of words that are specific to a language (French or Spanish) and words of a target language that have an orthographic neighbor that is more frequent in the other language. Concerning the lexical decision task, bilinguals process interlingual neighbors more slowly than specific words, for the French lists (dominant language) as well as for the Spanish lists (non-dominant language). For both languages, similar interferences were observed for interlingual orthographic neighbors in the language decision task. These results are discussed with reference to the bilingual interactive activation model (BIA) that proposes the existence of a non-selective initial access to two integrated lexicons. Key words : bilingualism, visual word recognition, interlingual orthographic neighbors, specific words.Résumé Nous avons manipulé la fréquence du voisinage orthographique interlangue dans une tâche de décision lexicale monolingue et de décision de langue. Dans la décision lexicale, les bilingues français/espagnol traitent plus lentement des mots qui possèdent un voisin orthographique plus fréquent dans l'autre langue (voisins orthographiques interlangues) que des mots spécifiques à une seule langue, à la fois dans les listes françaises et espagnoles. Pour les deux langues, nous obtenons des ralentissements similaires pour les voisins orthographiques interlangues dans la tâche de décision de langue. Les résultats sont interprétés dans le cadre du modèle d'Activation Interactive Bilingue (BIA). Mots clés : bilinguisme, reconnaissance visuelle de mots, voisins orthographiques interlangues, mots spécifiques.Font Noëlle, Lavaur J.-M. Effets de la fréquence du voisinage orthographique interlangue lors de la reconnaissance visuelle de mots chez les bilingues. In: L'année psychologique. 2004 vol. 104, n°3. pp. 377-405

Unraveling the Functions of Endogenous Receptor Oligomers in the Brain Using Interfering Peptide: The Example of D1R/NMDAR Heteromers

Decoding signaling pathways in different brain structures is crucial to develop pharmacological strategies for neurological diseases. In this perspective, the targeting of receptors by selective ligands is one of the classical therapeutic strategies. Nonetheless, this approach often results in a decrease of efficiency over time and deleterious side effects because physiological functions can be affected. An emerging concept has been to target mechanisms that fine-tune receptor signaling, such as heteromerization, the process by which physical receptor-receptor interaction at the membrane allows the reciprocal modulation of receptors' signaling. Because of the central role of the synergistic transmission mediated by dopamine (DA) and glutamate (Glu) in brain physiology and pathophysiology, heteromerization between DA and Glu receptors has received a lot of attention. However, the study of endogenous heteromers has been challenging because of the lack of appropriate tools. Over the last years, progress has been made in the development of techniques to study their expression in the brain, regulation and function. In this chapter, we provide a methodological framework for the design and use of interfering peptides to study endogenous receptor oligomers through the example of the dopamine type 1 receptor (D1R) and the GluN1 subunit of NMDA receptor heteromers

Antidepressive effects of targeting ELK-1 signal transduction

International audienceDepression, a devastating psychiatric disorder, is a leadingcause of disability worldwide. Current antidepressants addressspecific symptoms of the disease, but there is vast roomfor improvement1. In this respect, new compounds that actbeyond classical antidepressants to target signal transductionpathways governing synaptic plasticity and cellular resilienceare highly warranted2–4. The extracellular signal–regulatedkinase (ERK) pathway is implicated in mood regulation5–7, butits pleiotropic functions and lack of target specificity prohibitoptimal drug development. Here, we identified the transcriptionfactor ELK-1, an ERK downstream partner8, as a specificsignaling module in the pathophysiology and treatment ofdepression that can be targeted independently of ERK. ELK1mRNA was upregulated in postmortem hippocampal tissuesfrom depressed suicides; in blood samples from depressedindividuals, failure to reduce ELK1 expression was associatedwith resistance to treatment. In mice, hippocampal ELK-1 overexpressionper se produced depressive behaviors; conversely,the selective inhibition of ELK-1 activation prevented depression-like molecular, plasticity and behavioral states inducedby stress. Our work stresses the importance of target selectivityfor a successful approach for signal-transduction-basedantidepressants, singles out ELK-1 as a depression-relevanttransducer downstream of ERK and brings proof-of-conceptevidence for the druggability of ELK-1