Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours

J Comp Pathol. 2012 Aug-Oct;147(2-3):139-46. doi: 10.1016/j.jcpa.2012.01.021. Epub 2012 Apr 19.

Abstract

The peptidylarginine deiminase (PAD) enzyme family converts arginine residues in proteins to citrulline. In the canine mammary gland, PAD2 expression is first detected in epithelial cells in oestrus and becomes more widely expressed during dioestrus. PAD2 appears to modify nuclear histones, suggesting a role for the enzyme in chromatin remodelling and gene regulation. Recent evidence suggests that PAD2 plays a role in gene regulation in primary human breast epithelial cells. PAD2 may therefore be involved in gene regulation as it relates to mammary development, the oestrus cycle and potentially to neoplasia. The aim of the present study was to determine whether PAD2 expression was increased or decreased in mammary carcinoma compared with normal mammary tissue. A human mammary tissue microarray and archival surgical biopsy tissues from canine and feline mammary tumours were used to demonstrate differential expression of PAD2 in mammary carcinoma that appeared to be consistent across species. Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. Feline mammary carcinomas had complete loss of nuclear PAD2 expression. Loss of nuclear PAD2 expression may therefore represent a marker of progression towards more aggressive neoplasia.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / veterinary*
  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cats
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Disease Progression
  • Dogs
  • Female
  • Humans
  • Hydrolases / metabolism*
  • Mammary Glands, Animal / anatomy & histology
  • Mammary Glands, Animal / enzymology
  • Mammary Glands, Human / anatomy & histology
  • Mammary Glands, Human / enzymology
  • Mammary Neoplasms, Animal / enzymology
  • Mammary Neoplasms, Animal / pathology*
  • Protein-Arginine Deiminase Type 2
  • Protein-Arginine Deiminases
  • Species Specificity
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Hydrolases
  • PADI2 protein, human
  • Protein-Arginine Deiminase Type 2
  • Protein-Arginine Deiminases