Promyelocytic leukemia (PML) nuclear bodies are disorganized in colorectal tumors with total loss of major histocompatibility complex class I expression and LMP7 downregulation

Tissue Antigens. 2004 May;63(5):446-52. doi: 10.1111/j.0001-2815.2004.00204.x.

Abstract

The promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha (RARalpha) gene in acute promyelocytic leukemia (APL) and produces disruption of PML bodies. Wild-type PML localizes in the nucleus with a typical speckled pattern. PML bodies accumulate several proteins involved in multiple cellular pathways such as apoptosis, transcriptional regulation, and proteasomal degradation of ubiquitinated proteins. The ubiquitin-proteasome pathway at PML bodies is dependent on proteasome component recruitment. Proteasome components such as low-molecular weight proteins (LMPs) are frequently downregulated in different tumor tissues that present impaired major histocompatibility complex (MHC) class I expression. We have recently documented LMP7 downregulation in colorectal tumors with total loss of MHC class I antigen. An immunohistochemical study of PML protein in these tumors revealed a disrupted pattern of PML bodies in a nuclear diffuse form, as observed in APL cells. Therefore, the disruption of the PML bodies was clearly associated with LMP7 downregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Immunohistochemistry
  • Multienzyme Complexes / biosynthesis*
  • Multienzyme Complexes / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Proteasome Endopeptidase Complex
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • LMP7 protein
  • Proteasome Endopeptidase Complex