TY  - JOUR
A1  - Zanucco, Emanuele
A1  - Götz, Rudolf
A1  - Potapenko, Tamara
A1  - Carraretto, Irene
A1  - Ceteci, Semra
A1  - Ceteci, Fatih
A1  - Seeger, Werner
A1  - Savai, Rajkumar
A1  - Rapp, Ulf R.
T1  - Expression of B-RAF V600E in Type II Pneumocytes Causes Abnormalities in Alveolar Formation, Airspace Enlargement and Tumor Formation in Mice
JF  - PLOS ONE
N2  - Growth factor induced signaling cascades are key regulatory elements in tissue development, maintenance and regeneration. Perturbations of these cascades have severe consequences, leading to developmental disorders and neoplastic diseases. As a major function in signal transduction, activating mutations in RAF family kinases are the cause of human tumorigenesis, where B-RAF V600E has been identified as the prevalent mutant. In order to address the oncogenic function of B-RAF V600E, we have generated transgenic mice expressing the activated oncogene specifically in lung alveolar epithelial type II cells. Constitutive expression of B-RAF V600E caused abnormalities in alveolar epithelium formation that led to airspace enlargements. These lung lesions showed signs of tissue remodeling and were often associated with chronic inflammation and low incidence of lung tumors. The inflammatory cell infiltration did not precede the formation of the lung lesions but was rather accompanied with late tumor development. These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation.
KW  - obstructive pulmonary-disease
KW  - lung-cancer
KW  - somatic mutations
KW  - epithelial-cells
KW  - mouse models
KW  - protein
KW  - kinase
KW  - inflammation
KW  - activation
KW  - pathway
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137061
VL  - 6
IS  - 12
ER  - 
TY  - JOUR
A1  - Keller, Andreas
A1  - Leidinger, Petra
A1  - Vogel, Britta
A1  - Backes, Christina
A1  - ElSharawy, Abdou
A1  - Galata, Valentina
A1  - Mueller, Sabine C.
A1  - Marquart, Sabine
A1  - Schrauder, Michael G.
A1  - Strick, Reiner
A1  - Bauer, Andrea
A1  - Wischhusen, Jörg
A1  - Beier, Markus
A1  - Kohlhaas, Jochen
A1  - Katus, Hugo A.
A1  - Hoheisel, Jörg
A1  - Franke, Andre
A1  - Meder, Benjamin
A1  - Meese, Eckart
T1  - miRNAs can be generally associated with human pathologies as exemplified for miR-144*
JF  - BMC MEDICINE
N2  - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. 
Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. 
Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. 
Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
KW  - peripheral blood
KW  - microna profiles
KW  - disease
KW  - signature
KW  - expression
KW  - miRNA
KW  - microarray
KW  - biomarker
KW  - bioinformatics
KW  - lung-cancer
KW  - multiple sclerosis
KW  - gene
KW  - serum
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349
SN  - 1741-7015
VL  - 12
ER  -