Differential PAX3 functions in normal skin melanocytes and melanoma cells

Biochem Biophys Res Commun. 2011 Aug 12;411(4):832-7. doi: 10.1016/j.bbrc.2011.07.053. Epub 2011 Jul 23.

Abstract

The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as "stem" cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated "stem" cell like phenotype, PAX3 may contribute to melanoma development and progression.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Melanocytes / cytology
  • Melanocytes / metabolism*
  • Melanocytes / pathology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / physiology*
  • Skin / cytology
  • Skin / metabolism*
  • Skin / pathology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology

Substances

  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors