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  - Adam, Christian
A1  - Baeurle, Anne
A1  - Brodsky, Jeffrey L.
A1  - Schrama, David
A1  - Wipf, Peter
A1  - Becker, Jürgen Christian
A1  - Houben, Roland
T1  - The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma
N2  - Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future.
KW  - apoptosis
KW  - cancer treatment
KW  - cell staining
KW  - cultured fibroplasts
KW  - heat shock response
KW  - membrans proteins
KW  - polymerase chain reaction
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112795
ER  -