p53 regulation by TRP2 is not pervasive in melanoma

PLoS One. 2014 Jan 27;9(1):e87440. doi: 10.1371/journal.pone.0087440. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cloning, Molecular
  • Humans
  • Immunohistochemistry
  • Intramolecular Oxidoreductases / metabolism*
  • Melanoma / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction / physiology*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Intramolecular Oxidoreductases
  • dopachrome isomerase

Grants and funding

This work is supported by research grants from the German Cancer Aid (Melanoma Research Network) and the Interdisciplinary Center for Clinical Research (IZKF B-193) Würzburg. SH is a Else-Kröner-Research-Fellow. CPS and MM are supported by Medical Faculty scholarships of the University of Würzburg. This publication was funded by the German Research Foundation (DFG) and the University of Würzburg in the funding program Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.