72 research outputs found
Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation
<p>Abstract</p> <p>Background</p> <p>HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.</p> <p>Methods</p> <p>To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.</p> <p>Results</p> <p>Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate <it>in vitro </it>whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF<sup>-/-</sup>/Ink4a<sup>+/- </sup>mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.</p> <p>Conclusions</p> <p>The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.</p
Targeting HSP90 for cancer therapy
Heat-shock proteins (HSPs) are molecular chaperones that regulate protein folding to ensure correct conformation and translocation and to avoid protein aggregation. Heat-shock proteins are increased in many solid tumours and haematological malignancies. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of HSP90. Targeting HSP90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. This review provides an overview of the HSP chaperone machinery and the structure and function of HSP90. We also highlight the key oncogenic proteins that are regulated by HSP90 and describe how inhibition of HSP90 could alter the activity of multiple signalling proteins, receptors and transcriptional factors implicated in carcinogenesis
Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism
The Nature Index: A General Framework for Synthesizing Knowledge on the State of Biodiversity
The magnitude and urgency of the biodiversity crisis is widely recognized within
scientific and political organizations. However, a lack of integrated measures
for biodiversity has greatly constrained the national and international response
to the biodiversity crisis. Thus, integrated biodiversity indexes will greatly
facilitate information transfer from science toward other areas of human
society. The Nature Index framework samples scientific information on
biodiversity from a variety of sources, synthesizes this information, and then
transmits it in a simplified form to environmental managers, policymakers, and
the public. The Nature Index optimizes information use by incorporating expert
judgment, monitoring-based estimates, and model-based estimates. The index
relies on a network of scientific experts, each of whom is responsible for one
or more biodiversity indicators. The resulting set of indicators is supposed to
represent the best available knowledge on the state of biodiversity and
ecosystems in any given area. The value of each indicator is scaled relative to
a reference state, i.e., a predicted value assessed by each expert for a
hypothetical undisturbed or sustainably managed ecosystem. Scaled indicator
values can be aggregated or disaggregated over different axes representing
spatiotemporal dimensions or thematic groups. A range of scaling models can be
applied to allow for different ways of interpreting the reference states, e.g.,
optimal situations or minimum sustainable levels. Statistical testing for
differences in space or time can be implemented using Monte-Carlo simulations.
This study presents the Nature Index framework and details its implementation in
Norway. The results suggest that the framework is a functional, efficient, and
pragmatic approach for gathering and synthesizing scientific knowledge on the
state of biodiversity in any marine or terrestrial ecosystem and has general
applicability worldwide
Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer
A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence
The Principle of Rational Design of Drug Combination and Personalized Therapy Based on Network Pharmacology
- …