p73 is over-expressed in vulval cancer principally as the Delta 2 isoform

Br J Cancer. 2001 Nov 16;85(10):1551-6. doi: 10.1054/bjoc.2001.2138.

Abstract

p73 was studied in squamous cancers and precursor lesions of the vulva. Over-expression of p73 occurred commonly in both human papillomavirus (HPV)-positive and -negative squamous cell cancers (SCC) and high-grade premalignant lesions. Whereas expression in normal vulval epithelium was detected only in the basal and supra-basal layers, expression in neoplastic epithelium increased with grade of neoplasia, being maximal at both protein and RNA levels in SCC. p73 Delta 2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16(INK4a) in HPV-negative cases. There was a close correlation between expression of p73 and p14(ARF) in cancers with loss of p53 function. The frequent over-expression of p73 Delta 2 in neoplastic but not normal vulval epithelium, and its co-ordinate deregulation with other E2F-1 responsive genes suggests a role in the oncogenic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Mutation
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / metabolism*
  • Neoplasms, Squamous Cell / virology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Oncogene Proteins, Viral / biosynthesis
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • RNA, Neoplasm / biosynthesis
  • Transcriptional Activation
  • Tumor Protein p73
  • Tumor Suppressor Protein p14ARF / metabolism
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / virology
  • Vulvar Diseases / genetics
  • Vulvar Diseases / metabolism
  • Vulvar Neoplasms / genetics
  • Vulvar Neoplasms / metabolism*
  • Vulvar Neoplasms / virology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Protein Isoforms
  • RNA, Neoplasm
  • Tumor Protein p73
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • p73 protein, human