TY  - JOUR
A1  - Haferkamp, Sebastian
A1  - Hesbacher, Sonja
A1  - Weyandt, Gerhard
A1  - Vetter-Kauczok, Claudia S.
A1  - Becker, Jürgen C.
A1  - Motschenbacher, Stephanie
A1  - Wobser, Marion
A1  - Maier, Melissa
A1  - Schmid, Corinna P.
A1  - Houben, Roland
T1  - p53 regulation by TRP2 is not pervasive in melanoma
N2  - p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma.
KW  - melanomas
KW  - melanoma cell
KW  - cell staining
KW  - histology
KW  - reporter genes
KW  - apoptosis
KW  - immunohistochemistry techniques
KW  - tumor suppressor genes
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111396
ER  - 
TY  - JOUR
A1  - Houben, Roland
A1  - Hesbacher, Sonja
A1  - Schmid, Corinna P.
A1  - Kauczok, Claudia S.
A1  - Flohr, Ulrike
A1  - Haferkamp, Sebastian
A1  - Müller, Cornelia S. L.
A1  - Schrama, David
A1  - Wischhusen, Jörg
A1  - Becker, Jürgen C.
T1  - High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays
N2  - Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.
KW  - Krebs <Medizin>
KW  - Hautkrebs
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69012
ER  -