TY  - JOUR
A1  - Hönnemann, Jan
A1  - Sanz-Moreno, Adrian
A1  - Wolf, Elmar
A1  - Eilers, Martin
A1  - Elsässer, Hans-Peter
T1  - Miz1 Is a Critical Repressor of cdkn1a during Skin Tumorigenesis
JF  - PLoS One
N2  - The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15\(^{Ink4}\)), cdkn1a (p21\(^{Cip1}\)), and cdkn1c (p57\(^{Kip2}\)). Whether Miz1-mediated repression is important for control of cell proliferation in vivo and for tumor formation is unknown. Here we show that deletion of the Miz1 POZ domain, which is critical for Miz1 function, restrains the development of skin tumors in a model of chemically-induced, Ras-dependent tumorigenesis. While the stem cell compartment appears unaffected, interfollicular keratinocytes lacking functional Miz1 exhibit a reduced proliferation and an accelerated differentiation of the epidermis in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Tumorigenesis, proliferation and normal differentiation are restored in animals lacking cdkn1a, but not in those lacking cdkn2b. Our data demonstrate that Miz1-mediated attenuation of cell cycle arrest pathways via repression of cdkn1a has a critical role during tumorigenesis in the skin.
KW  - transcription factor MIZ-1
KW  - cell-cycle arrest
KW  - c-myc
KW  - tumor suppressor
KW  - cancer cells
KW  - POZ domain
KW  - P21
KW  - differentiation
KW  - P15(INK4B)
KW  - senescence
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133285
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Aukema, Sietse M.
A1  - Kreuz, Markus
A1  - Kohler, Christian W.
A1  - Rosolowski, Maciej
A1  - Hasenclever, Dirk
A1  - Hummel, Michael
A1  - Küppers, Ralf
A1  - Lenze, Diddo
A1  - Ott, German
A1  - Pott, Christiane
A1  - Richter, Julia
A1  - Rosenwald, Andreas
A1  - Szczepanowski, Monika
A1  - Schwaenen, Carsten
A1  - Stein, Harald
A1  - Trautmann, Heiko
A1  - Wessendorf, Swen
A1  - Trümper, Lorenz
A1  - Loeffler, Markus
A1  - Spang, Rainer
A1  - Kluin, Philip M.
A1  - Klapper, Wolfram
A1  - Siebert, Reiner
T1  - Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma
JF  - Haematologica
N2  - Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC+ lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC+-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC+ and BCL2(+)/MYC+ double-hit lymphomas. BCL2(+)/MYC+ double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC+ lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC+ lymphomas sharing various molecular characteristics.
KW  - Rituximab plus
KW  - cyclophsophamide
KW  - c-myc
KW  - gene expression
KW  - genomic aberrations
KW  - follicular lymphoma
KW  - prognostic factor
KW  - poor prognosis
KW  - grade 3B
KW  - distinct
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116882
SN  - 1592-8721
VL  - 99
IS  - 4
ER  -