TY  - JOUR
A1  - Hohenauer, Tobias
A1  - Berking, Carola
A1  - Schmidt, Andreas
A1  - Haferkamp, Sebastian
A1  - Senft, Daniela
A1  - Kammerbauer, Claudia
A1  - Fraschka, Sabine
A1  - Graf, Saskia Anna
A1  - Irmler, Martin
A1  - Beckers, Johannes
A1  - Flaig, Michael
A1  - Aigner, Achim
A1  - Höbel, Sabrina
A1  - Hoffmann, Franziska
A1  - Hermeking, Heiko
A1  - Rothenfusser, Simon
A1  - Endres, Stefan
A1  - Ruzicka, Thomas
A1  - Besch, Robert
T1  - The neural crest transcription factor Brn3a is expressed in melanoma and required for cell cycle progression and survival
JF  - EMBO Molecular Medicine
N2  - Pigment cells and neuronal cells both are derived from the neural crest. Here, we describe the Pit-Oct-Unc (POU) domain transcription factor Brn3a, normally involved in neuronal development, to be frequently expressed in melanoma, but not in melanocytes and nevi. RNAi-mediated silencing of Brn3a strongly reduced the viability of melanoma cell lines and decreased tumour growth in vivo. In melanoma cell lines, inhibition of Brn3a caused DNA double-strand breaks as evidenced by Mre11/Rad50-containing nuclear foci. Activated DNA damage signalling caused stabilization of the tumour suppressor p53, which resulted in cell cycle arrest and apoptosis. When Brn3a was ectopically expressed in primary melanocytes and fibroblasts, anchorage-independent growth was increased. In tumourigenic melanocytes and fibroblasts, Brn3a accelerated tumour growth in vivo. Furthermore, Brn3a cooperated with proliferation pathways such as oncogenic BRAF, by reducing oncogene-induced senescence in non-malignant melanocytes. Together, these results identify Brn3a as a new factor in melanoma that is essential for melanoma cell survival and that promotes melanocytic transformation and tumourigenesis.
KW  - oncogene-induced senescence
KW  - BRN-3A
KW  - DNA
KW  - DNA damage
KW  - tumourigenesis
KW  - P53
KW  - in-vitro
KW  - neural crest factors
KW  - family
KW  - apoptosis
KW  - melanoma
KW  - BRAF mutations
KW  - domain
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122193
SN  - 1757-4676
VL  - 5
ER  - 
TY  - JOUR
A1  - Meier, Friedegund
A1  - Gross, Eva
A1  - Klotz, Karl-Norbert
A1  - Ruzicka, Thomas
T1  - Leukotriene B4 receptors on neutrophils in patients with psoriasis and atopic exzema
N2  - Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. Elevated concentrations of the chemoattractant eicosanoid leukotriene B4 (L TB4) are present in psoriatic skin. Its chemotactic activity is mediated via high affinity receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the LTB4 receptor density or affinity (or both). No significant difference was found between patients with psoriasis, healthy controls and patients with another inflammatory dermatosis (atopic eczema) with regard to the binding parameters of LTB4 receptors on PMNL. Our findings suggest that PMNL accumulation in psoriatic skin may be the result of an excess of cutaneous  hemoattractant rather than the increased readiness of psoriatic PMNL to migrate towards L TB4 due to altered LTB4 receptor density or affinity.
KW  - Dermatologie
KW  - Venerologie
KW  - Pharmakologie
KW  - Pharmazie
KW  - LTB4 receptor
KW  - neutrophils
KW  - psoriasis
KW  - atopic eczema
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86265
ER  -