1,721,020 research outputs found
Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition.
No full textPancreatic cancer is one of the deadliest cancers due to early rapid metastasis and chemoresistance. Recently, epithelial to mesenchymal transition (EMT) was shown to play a key role in the pathogenesis of pancreatic cancer. To understand the role of caveolin-1 (Cav-1) in EMT, we over-expressed Cav-1 in a pancreatic cancer cell line, Panc 10.05, that does not normally express Cav-1. Here, we show that Cav-1 expression in pancreatic cancer cells induces an epithelial phenotype and promotes cell-cell contact, with increased expression of plasma membrane bound E-cadherin and beta-catenin. Mechanistically, Cav-1 induces Snail downregulation and decreased activation of AKT, MAPK and TGF-beta-Smad signaling pathways. In vitro, Cav-1 expression reduces cell migration and invasion, and attenuates doxorubicin-chemoresistance of pancreatic cancer cells. Importantly, in vivo studies revealed that Cav-1 expression greatly suppresses tumor formation in a xenograft model. Most interestingly, Panc/Cav-1 tumors displayed organized nests of differentiated cells that were totally absent in control tumors. Confirming our in vitro results, these nests of differentiated cells showed reexpression of E-cadherin and beta-catenin at the cell membrane. Thus, we provide evidence that Cav-1 functions as a crucial modulator of EMT and cell differentiation in pancreatic cancer
Caveolin-1-Deficient Mice Have An Increased Mammary Stem Cell Population, with Upregulation of Wnt / ?-Catenin Signaling
No full textCaveolin-1 Deficiency (-/-)Conveys Cell Autonomous Defects in Mammary Epithelia, with Abnormal 3D Lumen Formation, EGF-independent Growth, and Increased Branching Capacity
No full textMEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma.
No full textWe reported previously that the disruption of c-Myc
through mitogen-activated protein kinase kinase (MEK)/
extracellular signal-regulated kinase (ERK) inhibition blocks
the expression of the transformed phenotype in the
embryonal rhabdomyosarcoma (ERMS) cell line (RD),
thereby inducing myogenic differentiation in vitro. In this
article, we investigate whether MEK/ERK inhibition, by the
MEK/ERK inhibitor U0126, affects c-Myc protein level and
growth of RMS tumor in an in vivo xenograft model.
U0126 significantly reduced RMS tumor growth in RD
cell line-xenotransplanted mice. Immunobiochemical and
immunohistochemical analysis showed (a) phospho-active
ERK levels were reduced by U0126 therapy and unaltered
in normal tissues, (b) phospho-Myc and c-Myc was reduced
commensurate with phospho-ERK inhibition, and (c)
reduction in Ki-67 and endothelial (CD31) marker expression.
These results indicate that MEK/ERK inhibition
affects growth and angiogenic signals in tumor. The RDM1
cultured xenograft tumor-derived cell line and the
ERMS cell line TE671 responded to U0126 by arresting
growth, down-regulating c-Myc, and initiating myogenesis.
All these results suggest a tight correlation of MEK/
ERK inhibition with c-Myc down-regulation and arrest of
tumor growth. Thus, MEK inhibitors may be investigated
for a signal transduction-based targeting of the c-Myc as a
therapeutic strategy in ERMS. [Mol Cancer Ther 2009;
8(3):543–51
Clinical and translational implications of the caveolin gene family: lessons from mouse models and human genetic disorders.
No full textMolecular genetics of the caveolin gene family: Implications for human cancers, Diabetes, Alzheimer disease, and muscular dystrophy
No full textLoss of Caveolin-1 Causes the Hyper-proliferation of Intestinal Crypt Stem Cells, with Increased Sensitivity to Whole Body -Radiation
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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