p73 is over-expressed in vulval cancer principally as the Delta 2 isoform.
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.
O'Nions
J
J
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG .
Brooks
L A
LA
Sullivan
A
A
Bell
A
A
Dunne
B
B
Rozycka
M
M
Reddy
A
A
Tidy
J A
JA
Evans
D
D
Farrell
P J
PJ
Evans
A
A
Gasco
M
M
Gusterson
B
B
Crook
T
T
D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014845:Vulvar Diseases / Q000235:genetics / Q000378:metabolism; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D020033:Protein Isoforms; D012334:RNA, Neoplasm; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16