Expression of TRPC6 channels in human epithelial breast cancer cells

<p>Abstract</p> <p>Background</p> <p>TRP channels have been shown to be involved in tumour generation and malignant growth. However, the expression of these channels in breast cancer remains unclear. Here we studied the expression and function of endogenous TRPC6 channels in a breast cancer cell line (MCF-7), a human breast cancer epithelial primary culture (hBCE) and in normal and tumour breast tissues.</p> <p>Methods</p> <p>Molecular (Western blot and RT-PCR), and immunohistochemical techniques were used to investigate TRPC6 expression. To investigate the channel activity in both MCF-7 cells and hBCE we used electrophysiological technique (whole cell patch clamp configuration).</p> <p>Results</p> <p>A non selective cationic current was activated by the oleoyl-2-acetyl-sn-glycerol (OAG) in both hBCE and MCF-7 cells. OAG-inward current was inhibited by 2-APB, SK&F 96365 and La³⁺. TRPC6, but not TRPC7, was expressed both in hBCE and in MCF-7 cells. TRPC3 was only expressed in hBCE. Clinically, TRPC6 mRNA and protein were elevated in breast carcinoma specimens in comparison to normal breast tissue. Furthermore, we found that the overexpression of TRPC6 protein levels were not correlated with tumour grades, estrogen receptor expression or lymph node positive tumours.</p> <p>Conclusion</p> <p>Our results indicate that TRPC6 channels are strongly expressed and functional in breast cancer epithelial cells. Moreover, the overexpression of these channels appears without any correlation with tumour grade, ER expression and lymph node metastasis. Our findings support the idea that TRPC6 may have a role in breast carcinogenesis.</p

Notre microbiote intestinal, cible collatérale des pesticides : focus sur les effets du chlorpyrifos: L’impact des pesticides sur notre santé est de plus en plus questionné.

International audienc

Impact d'une exposition chronique au chlorpyriphos sur le développement, la maturation de l'intestin et le microbiote (approches in vivo (rat) et in vitro (SHIME®))

L exposition aux résidus de pesticides par voie alimentaire rend le système digestif, premier organe en contact avec ces contaminants, particulièrement vulnérable. Partant de l hypothèse que le contact in utero ou en période postnatale avec un pesticide, est un agent perturbateur de l homéostasie corporelle au cours du développement, nous avons étudié différents paramètres au sein du tractus intestinal afin de déterminer si et de quelle manière la maturation et le fonctionnement du système digestif peuvent être altérés suite à un contact avec un pesticide. Cette étude a été réalisée sur modèle animal (rat) par exposition continue à de faibles doses de chlorpyriphos (CPF) pendant toute la durée de la gestation ainsi qu au cours de la vie néonatale (périodes de développement et de maturation du système digestif). Les animaux ont été étudiés au sevrage (J21) et à 60 jours (J60). Une étude in vitro a été réalisée de façon complémentaire au sein d'un système digestif artificiel modélisant l écosystème microbien intestinal humain (SHIME®). Nos résultats mettent en évidence que l ingestion chronique à faible dose de chlorpyriphos lors du développement du raton provoque une dysbiose intestinale et une translocation bactérienne accrue vers les organes stériles. Ces paramètres soulignent des répercussions fonctionnelles chez l individu exposé in utero et par la lactation notamment une perméabilité intestinale augmentée (altération de l expression de certaines protéines de complexes jonctionnels) corrélée à des observations morphométriques tissulaires. L'altération du système digestif par le chlorpyriphos est importante chez un animal immature (J21) et persiste dans le temps (J60) même si ces effets sont de moindre importance. Ces effets délétères d une exposition chronique même à faible dose de pesticide sur le système digestif peuvent laisser craindre des effets à plus long terme et/ou avec des répercussions sur d autres fonctions physiologiquesHumans are exposed on a daily basis to pesticide residues that contaminate the environment and food products. Given that the digestive tract is the first organ to contact food, it is particularly vulnerable to the harmful effects of food contaminants. When exposure takes place during fetal and postnatal development, the impacts may be particularly harmful. We studied a variety of different parameters within the intestinal tract, in order to determine whether and how contact with a pesticide can alter the maturation and function of the digestive system. Animal models (rats) were continuously exposed to low doses of chlorpyrifos (CPF) during the entire gestational and neonatal periods (during which the digestive system develops and matures). The pup were studied at weaning (D21) and at 60 days of age (D60). In parallel, an in vitro study was carried out by using an artificial model of the human intestinal microbial ecosystem (the SHIME® device). Our data demonstrate that chronic ingestion of low-dose CPF during a pup's development is associated with intestinal dysbiosis and elevated bacterial translocation to sterile organs. Our results highlighted functional impairments in animals exposed to CPF in utero and during lactation, including increased intestinal permeability (as evidenced by the enhanced passage of FITC-dextran, and altered expression of tight junction proteins). Furthermore, these functional impairments were correlated with morphological changes in the intestinal tissues. The CPF-associated changes in the digestive system were more marked in immature animals (D21) but persisted (albeit at a lower intensity) over time (up to D60). Lastly, we hypothesize that the harmful effects of chronic, low-dose exposure to CPF may impact other physiological functions.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Bifidogenic effect of a wheat arbinoxylan (MC-AX) is observed across two animal models, a stimulated human intestine model (SHIMES®) and a clinical study.

International audienceBifidogenic effect of a wheat arabinoxylan (MC-AX) is observed across two animal models, a simulated human intestine model (SHIME®) and a clinical study

Bifidogenic effect of a wheat arbinoxylan (MC-AX) is observed across two animal models, a stimulated human intestine model (SHIMES®) and a clinical study.

International audienceBifidogenic effect of a wheat arabinoxylan (MC-AX) is observed across two animal models, a simulated human intestine model (SHIME®) and a clinical study