In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-09-26)
Kurzfassung:
TFE -fusion renal cell carcinomas ( TFE -fusion RCCs ) are caused by chromosomal translocations that lead to overexpression of the TFEB and TFE3 genes ( Kauffman et al., 2014 ). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system ( Kauffman et al., 2014 ). Here, we show that kidney-specific TFEB overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both TFEB- and TFE3 -mediated human kidney tumors. Analysis of kidney samples revealed transcriptional induction and enhanced signaling of the WNT β-catenin pathway. WNT signaling inhibitors normalized the proliferation rate of primary kidney cells and significantly rescued the disease phenotype in vivo. These data shed new light on the mechanisms underlying TFE- fusion RCCs and suggest a possible therapeutic strategy based on the inhibition of the WNT pathway.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.17047.001
DOI:
10.7554/eLife.17047.002
DOI:
10.7554/eLife.17047.003
DOI:
10.7554/eLife.17047.004
DOI:
10.7554/eLife.17047.005
DOI:
10.7554/eLife.17047.006
DOI:
10.7554/eLife.17047.007
DOI:
10.7554/eLife.17047.008
DOI:
10.7554/eLife.17047.009
DOI:
10.7554/eLife.17047.010
DOI:
10.7554/eLife.17047.011
DOI:
10.7554/eLife.17047.012
DOI:
10.7554/eLife.17047.013
DOI:
10.7554/eLife.17047.014
DOI:
10.7554/eLife.17047.015
DOI:
10.7554/eLife.17047.016
DOI:
10.7554/eLife.17047.017
DOI:
10.7554/eLife.17047.018
DOI:
10.7554/eLife.17047.019
DOI:
10.7554/eLife.17047.020
DOI:
10.7554/eLife.17047.021
DOI:
10.7554/eLife.17047.022
DOI:
10.7554/eLife.17047.023
DOI:
10.7554/eLife.17047.024
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2016
ZDB Id:
2687154-3
