Matrix metalloproteinase-2 and -9 secretion by the human JAR choriocarcinoma cell line is stimulated by TNF-alpha.

International audienceThe JAR choriocarcinoma cell line share many of the characteristics of early placental trophoblast cells including the invasion properties. Matrix metallo-proteinases (MMPs), the main actors of matrix prote-olysis, are involved in normal invasion as well as in the invasive character of tumor cells and the metas-tase formation. Tumor necrosis factor-α (TNF-α) is present in the placental environment and TNF-α levels are elevated in some placental pathologies. In the present work, we addressed whether TNF-α is a modulator of JAR cell MMP secretion. Following TNF-α stimulation, zymographic analysis showed the increased secretion of the active form of MMP-2 and to a lesser extent proMMP-2 and MMP-9. In addition, MMP-2 gene expression only increased slightly whereas MMP-9 and TIMP-1 transcripts were undetectable. This suggests that TNF-α may modulate the secretion of MMPs independently of MMP gene expression control

Transposable elements and human cancer: A causal relationship?

International audienceTransposable elements are present in almost all genomes including that of humans. These mobile DNA sequences are capable of invading genomes and their impact on genome evolution is substantial as they contribute to the genetic diversity of organisms. The mobility of transposable elements can cause deleterious mutations, gene disruption and chromosome rearrangements that may lead to several pathologies including cancer. This mini-review aims to give a brief overview of the relationship that transposons and retrotransposons may have in the genetic cause of human cancer onset, or conversely creating protection against cancer. Finally, the cause of TE mobility may also be the cancer cell environment itself

Vectors for gene therapy: A place for DNA transposon

International audienceGene therapy offers important perspectives in current and future medicine but suffers from imperfect vectors for the delivery of the therapeutic gene. Most preclinical and clinical trials have been based on the use of viral vectors, which have evident advantages but also some serious disadvantages. In the past decade the use of DNA transposon-based systems for gene delivery has emerged as a non-viral alternative. DNA transposon vector engineering remains largely in a preclinical phase but some interesting results have been obtained. This mini-review aims to provide the current state of the art on DNA transposon vectors used in a gene therapy perspective

Caractérisation de l'expression et de la fonction du facteur de transcription Nrf3 dans les cellules humaines

En collaboration avec V. Blank (Université McGill, Montréal), nous avons montré que le facteur de transcription Nrf3 est fortement exprimé, au niveau ARN et protéine, dans les cellules du placenta humain et les lignées de choriocarcinomes. De plus l'expression de Nrf3 est stimulée par le TNF-α dans les lignées de choriocarcinome et d'autres lignées tumorales humaines. Au niveau fonctionnel, nous avons montré par retard de migration électrophorétique que Nrf3 peut s'associer à toutes les petites protéines Maf connues (MafF, MafG, MafK) pour se lier à l'ADN. Après avoir cloné le promoteur de NRF3, nous avons recherché un rôle de Nrf3 par une approche d'interférence d'ARN dans plusieurs modèles de lignées tumorales humaines

Transposable Elements in Cancer and Other Human Diseases

International audienceTransposable elements (TEs) are mobile DNA sequences representing a substantial fraction of most genomes. Through the creation of new genes and functions, TEs are important elements of genome plasticity and evolution. However TE insertion in human genomes may be the cause of genetic dysfunction and alteration of gene expression contributing to cancer and other human diseases. Besides the chromosome rearrangements induced by TE repeats, this mini-review shows how gene expression may be altered following TE insertion, for example by the creation of new polyadenylation sites, by the creation of new exons (exonization), by exon skipping and by other modification of alternative splicing, and also by the alteration of regulatory sequences. Through the correlation between TE mobility and the methylation status of DNA, the importance of chromatin regulation is evident in several diseases. Finally this overview ends with a brief presentation of the use of TEs as biotechnology tools for insertional mutagenesis screening and gene therapy with DNA transposons

Mobile Elements in the Human Genome: Implications for Disease

International audienceTransposable elements (TEs) are mobile DNA sequences that represent a great portion of the human genome. TEs are divided into retrotransposons, the more abundant, and DNA transposons, which differ by their structure and transposition mechanisms. The major LINE-1 and Alu elements represent about one-third of the human genome and are responsible for several chromosomal rearrangements, gene deletion, insertional mutagenesis as well as RNA splicing alteration and epigenetic regulation. DNA transposons and human endogenous retroviruses are also a source of genetic alterations. Consequently, TE insertion and mobility lead to human diseases, among which are cancer, hematologic disease, metabolic disease, neurodegenerescence and neurologic and psychiatric diseases. The examples of TE-related diseases presented herein aim to highlight the interest of increasing our knowledge of TEs through extensive genomic approaches, which may lead to new potential diagnostic markers of diseases

Algae and Microalgae and Their Bioactive Molecules for Human Health

The algae and microalgae are an extremely diverse group of organisms that contain many bioactive molecules, including pigments, polyunsaturated fatty acids, polysaccharides, polyphenol, etc [...

The Janus Face of Lipids in Human Breast Cancer: How Polyunsaturated Fatty Acids Affect Tumor Cell Hallmarks

International audienceFor several years, lipids and especially n − 3 and n − 6 polyunsaturated fatty acids (PUFAs) receive much attention in human health. Epidemiological studies tend to correlate a PUFA-rich diet with a reduced incidence of cancer, including breast cancer. However, the molecular and cellular mechanisms supporting the effect of PUFAs in breast cancer cells remain relatively unknown. Here, we review some recent progress in understanding the impact that PUFA may have on breast cancer cell proliferation, apoptosis, migration, and invasion. While most of the results obtained with docosahexaenoic acid and/or eicosapentaenoic acid show a decrease of tumor cell proliferation and/or aggressivity, there is some evidence that other lipids, which accumulate in breast cancer tissues, such as arachidonic acid may have opposite effects. Finally, lipids and especially PUFAs appear as potential adjuvants to conventional cancer therapy

Involvement of Nitric Oxide Synthase in antiproliferative activity of macrophages: Induction of the enzyme requires two different kinds of signal acting synergistically

International audienceActivated rodent macrophages inhibit microorganism and tumour cell growth through a high output of nitric oxide; generated by an isoform of nitric oxide synthase which is induced, for example, in murine macrophages, by concomitant stimulation with interferon-y (IFN-y) and lipopolysaccharide (LPS). We show here that LPS could be replaced as a co-stimulant by the mycobacterial derivative muramyl dipeptide (MDP) in macrophages, and by interleukin-I (IL-1) in EMT-6 adenocarcinoma cells. Moreover, our results indicate that nitric oxide synthase RNA synthesis required either simultaneous or sequential exposure to IFN-y and MDP/IL-1; whereas exposure to MDP/IL-1 followed by exposure to IFN-y was ineffective. Thus, two kinds of signal could be distinguished: IFN-y on the one hand, acting first in an irreversible way, and LPS, MDP, IL-1 on the other hand, which seemed to be permanently required for continuous transcription of the nitric oxide synthase gene