TBX2 expression is regulated by PAX3 in the melanocyte lineage

Pigment Cell Melanoma Res. 2013 Jan;26(1):67-77. doi: 10.1111/pcmr.12029. Epub 2012 Nov 21.

Abstract

The paired box homeotic gene 3 (PAX3) is a crucial regulator for the maintenance of melanocytic progenitor cells and has a poorly defined role in melanoma. To understand how PAX3 affects melanocyte and melanoma proliferation, we identified potential PAX3 downstream targets through gene expression profiling. Here, we identify T-box 2 (TBX2), a key developmental regulator of cell identity and an antisenescence factor in melanoma, as a directly regulated PAX3 target. We also found that TBX2 is involved in the survival of melanoma cells and is overexpressed in some melanoma specimens. The identification of TBX2 as a target for PAX3 provides a key insight into how PAX3 may contribute to melanoma evolution and may provide opportunities for prosenescence therapeutic intervention aimed at disrupting the ability of PAX3 to regulate TBX2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage* / genetics
  • Cell Proliferation
  • Cell Survival / genetics
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanocytes / metabolism*
  • Melanocytes / pathology
  • Melanoma / genetics
  • Melanoma / pathology
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • Up-Regulation / genetics

Substances

  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • T-Box Domain Protein 2
  • T-Box Domain Proteins
  • Pax3 protein, mouse