Galectin genes: regulation of expression.

In this review we have summarized the more recent studies on the expression of mammalian galectins. One interesting observation that can be made is that in most of microarrays and/or differential display analysis performed in recent years one or more galectins have been picked up. From a critical evaluation of the pertinent studies the main conclusion that can be drawn is that, although it is not yet clear whether the 14 galectins identified so far have functions in common, a striking common feature of all galectins is the strong modulation of their expression during development, differentiation stages and under different physiological or pathological conditions. This suggests that the expression of different galectins is finely tuned and possibly coordinated. In spite of these observations it is rather unexpected that very few studies have been performed on the molecular mechanisms governing the activity of galectin genes

Structure of the rat insulin-like growth factor II transcriptional unit: heterogeneous transcripts are generated from two promoters by use of multiple polyadenylation sites and differential ribonucleic acid splicing.

The rat insulin-like growth factor II (rIGF-II) gene, which exists as a single copy in the genome, is expressed as a multitranscript family of mRNA molecules ranging in size from 4.6 to 1 kilobases. Part of this heterogeneity can be ascribed to the presence of two different promoters, each transcribing alternative 5'-noncoding regions which are spliced to common coding exons. In the present study we use a combination of DNA sequence analysis of the gene, mapping of the mRNA molecules by Northern analysis and ribonuclease protection experiments, and DNA sequence analysis of cDNA clones complementary to different regions of the genome to establish the structure of several rIGF-II mRNA species. These results indicate that RNA heterogeneity also arises from the use of different polyadenylation sites. In addition, a variant 2 kilobases RNA was observed that was colinear with the distal 1700 base pairs of the 3147 base pair long exon 3, and may arise by alternative RNA splicing. These posttranscriptional modifications of RNAs arising from the rIGF-II transcription unit may generate molecules with different functional potential

Structure and expression of the rat insulin-like growth factor II (rIGF-II) gene. rIGF-II RNAs are transcribed from two promoters.

Insulin-like growth factor II (IGF-II) is a mitogenic polypeptide present in rat plasma at high levels during fetal and early postnatal life and is believed to play an important, although as yet undefined, role in fetal development. Both in humans and rats, expression of the IGF-II gene results in the appearance of several mRNA species. In the present study, cDNA and synthetic oligonucleotide probes were used to isolate and characterize the rat IGF-II gene from genomic libraries. The rat IGF-II gene extends over 12 kilobase pairs and contains two 5'-noncoding exons and three protein-coding exons. The two 5' exons represent alternative 5' regions of different mRNA molecules and are expressed from two distinct promoters. The two promoters are transcribed with different efficiencies but exhibit similar tissue-specific expression and regulation with developmental ag

The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility

Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85PI3K) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in the p85PI3K that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used p85PI3K mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of p85PI3K S83 modulates the formation of the p85PI3K /IRS-1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the p85PI3K S83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the p85PI3K S83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model

Reactive oxygen species regulate the levels of dual oxidase (Duox1-2) in human neuroblastoma cells.

Dual Oxidases (DUOX) 1 and 2 are efficiently expressed in thyroid, gut, lung and immune system. The function and the regulation of these enzymes in mammals are still largely unknown. We report here that DUOX 1 and 2 are expressed in human neuroblastoma SK-N-BE cells as well as in a human oligodendrocyte cell line (MO3-13) and in rat brain and they are induced by platelet derived growth factor (PDGF). The levels of DUOX 1 and 2 proteins and mRNAs are induced by reactive oxygen species (ROS) produced by the membrane NADPH oxidase. As to the mechanism, we find that PDGF stimulates membrane NADPH oxidase to produce ROS, which stabilize DUOX1 and 2 mRNAs and increases the levels of the proteins. Silencing of gp91(phox) (NOX2), or of the other membrane subunit of NADPH oxidase, p22(phox), blocks PDGF induction of DUOX1 and 2. These data unravel a novel mechanism of regulation of DUOX enzymes by ROS and identify a circuitry linking NADPH oxidase activity to DUOX1 and 2 levels in neuroblastoma cells.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe