Histology and histopathology Vol.26, nº5 (2011)
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- PublicationOpen AccessInduction of pluripotency in primordial germ cells(Murcia: F. Hernández, 2011) Kimura, Tohru; Nakano, ToruSummary. Primordial germ cells (PGCs) are the founder cells of all gametes. PGCs differentiate from pluripotent epiblasts cells by mesodermal induction signals during gastrulation. Although PGCs are unipotent cells that eventually differentiate into only sperm or oocytes, they dedifferentitate to pluripotent stem cells known as embryonic germ cells (EGCs) in vitro and give rise to testicular teratomas in vivo, which indicates a “metastable” differentiation state of PGCs. We have shown that an appropriate level of phosphoinositide-3 kinase (PI3K)/Akt signaling, balanced by positive and negative regulators, ensures the establishment of the male germ lineage by preventing its dedifferentiation. Specifically, hyper-activation of the signal leads to testicular teratomas and enhances EGC derivation efficiency. In addition, PI3K/Akt signaling promotes PGC dedifferentiation via inhibition of the tumor suppressor p53, a downstream molecule of the PI3K/Akt signal. On the other hand, Akt activation during mesodermal differentiation of embryonic stem cells (ESCs) generates PGC-like pluripotent cells, a process presumably induced through equilibrium between mesodermal differentiation signals and dedifferentiationinducing activity of Akt. The transfer of these cells to ESC culture conditions results in reversion to an ESClike state. The interconversion between ESC and PGClike cells helps us to understand the metastability of PGCs. The regulatory mechanisms of PGC dedifferentiation are discussed in comparison with those involved in the dedifferentiation of testicular stem cells, ESC pluripotency, and somatic nuclear reprogramming.
- PublicationOpen AccessAkt1 and Akt2: Differentiating the aktion(Murcia: F. Hernández, 2011) Heron-Milhavet, Lisa; Khouya, Nabil; Fernandez, Anne; Lamb, Ned J.Kinases of the Akt family are integral and essential components in growth factor signaling pathways activated downstream of the membrane bound phospho-inositol-3 kinase. In light of strong homologies in the primary amino acid sequence, the three Akt kinases were long surmised to play redundant and overlapping roles in insulin signaling across the spectra of cell and tissue types. Over the last 10 years, work using mouse knockout models, cell specific inactivation, and more recently targeted gene inactivation, has brought into question the redundancy within Akt kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. Here we concentrate on the differential roles played by Akt1 and Akt2 in a variety of cellular processes and in particular during cancer biogenesis. In this overview, we illustrate that while Akt1 and 2 are often implicated in many aspects of cellular transformation, the two isoforms frequently act in a complementary opposing manner. Furthermore, Akt1 and Akt2 kinases interact differentially with modulating proteins and are necessary in relaying roles during the evolution of cancers from deregulated growth into malignant metastatic killers. These different actions of the two isoforms point to the importance of treatments targeting isoform specific events in the development of effective approaches involving Akt kinases in human disease.
- PublicationOpen AccessLipid droplet associated proteins:an emerging role in atherogenesis(Murcia: F. Hernández, 2011) Buers, Insa; Hofnagel, Oliver; Ruebel, Anneke; Severs, Nicholas J.; Robenek, HorstCoronary heart disease and stroke, caused by rupture of atherosclerotic plaques in the arterial wall, are the major causes of death in industrialized countries. A key event in the pathogenesis of atherosclerosis is the transformation of smooth muscle cells and in particular of macrophages into foam cells, a result of massive accumulation of lipid droplets. It is well known that the formation of these lipid droplets is a result of the uninhibited uptake of modified lipoproteins by scavenger receptors. However, only more recently has it become apparent that a special set of lipid droplet associated proteins - the PAT protein family (perilipin, adipophilin, TIP47, S3-12 and OXPAT) - is fundamental to the formation, growth, stabilization and functions of lipid droplets. Here we review recent findings and assess the current state of knowledge on lipid droplets and their PAT proteins in atherogenesis.
- PublicationOpen AccessPeg-and-socket junctions between smooth muscle cells and endothelial cells in femoral veins are stimulated to angiogenesis by prostaglandin E2 and glycerols(Murcia: F. Hernández, 2011) Díaz-Flores Jr., L.; Gutiérrez, R.; Sáez, F.J.; Valladares, F.; Villar, J.; Díaz-Flores, L.; Madrid Cuevas, Juan FranciscoThe administration of prostaglandin (PG) E2, triacetylglycerol and glycerol induce the formation of numerous vascular buds arising from the femoral vein, as previously demonstrated by our group. In the present study, a great number of peg-and-socket junctions (PSJs) between smooth muscle cells (SMCs) (providing the pegs) and ECs (forming the sockets) were demonstrated. At the first stage, days 1 to 3, PSJs connect subendothelial penetrating processes from activated SMCs with activated ECs of the intima. Subsequently, during angiogenesis (days 4 to 6), SMCs, showing transitional aspects with pericytes, also form PSJs with intimal ECs, but also new PSJs between SMCs and sprouting ECs in the media layer were now observed. Immunohistochemically, α-smooth muscle actin (α- SMA) and H-caldesmon are positive in the cytoplasm of the SMCs, showing a higher expression in pegs. Desmin, however, although it is also positive in the cytoplasm of the SMCs, is negative in the pegs. The expression of CD34 in ECs reveals abundant positive folding that appears to correspond to the sockets. The peculiar expression of caldesmon, whose isoforms may contribute to the regulation of cell motility, and to vasculogenesis and angiogenesis, may have a role in the different mechanisms by which PSJs act in the vein wall.
- PublicationOpen AccessCytoplasmic expression of p33ING1b is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma(Murcia: F. Hernández, 2011) Li, Xiao-Han; Noguchi, Akira; Nishida, Takeshi; Takahashi, Hiroyuki; Zheng, Yang; Yang, Xiang-Hong; Masuda, Shinji; Kikuchi, Keiji; Takano, YasuoSummary. To clarify the role of p33ING1b in tumorigenesis and progression of head and neck squamous cell carcinoma (HNSCC), we examined the expression and subcellular localization of p33ING1b in 214 HNSCC cases in parallel with 60 dysplasia samples and 48 normal epithelium samples by immunohistochemistry, and analyzed correlations of expression of p33ING1b in HNSCC cases with clinicopathological variables, apototic index and expression of 14-3-3η, p300, p21 and PCNA. Although 12% of HNSCC cases lost expression of p33ING1b, most cases of HNSCC retained expression of p33ING1b with levels similar to those in non-cancerous epithelia. Nuclear expression of p33ING1b was significantly decreased in HNSCC compared to normal epithelia. In contrast, cytoplasmic expression of p33ING1b was found to be significantly higher in HNSCC. An abundance of p33ING1b in cytoplasm positively correlated with poor differentiation and tumor progression. Corresponding to those clinicopathogical features, high expression of p33ING1b in the cytoplasm correlated with PCNA labelling index but in contrast, that in the nuclei correlated with apoptosis. In nuclei, p33ING1b is coexpressed with p300 and p21, implying its roles in tumor suppression. Elevated expression of 14-3-3η was associated with cytoplasmic expression of p33ING1b and immunofluorescence study suggested association of p33ING1b and 14-3-3η. Among three cell lines derived from oral SCC, poorly-differentiated SAS cells showed a relatively high expression of p33ING1b in cytoplasm with
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