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PMID: 11720444 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

British journal of cancer ·Vol. 85 ·No. 10 ·2001-11-16 ·Pages 1551-6

O'Nions J, Brooks LA, Sullivan A, Bell A, Dunne B, Rozycka M, Reddy A, Tidy JA, Evans D, Farrell PJ, Evans A, Gasco M, Gusterson B, Crook T

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.

MeSH Terms
Cyclin-Dependent Kinase Inhibitor p16/genetics DNA Methylation DNA-Binding Proteins/biosynthesis,genetics,immunology Female Genes, Tumor Suppressor Humans Immunohistochemistry Mutation Neoplasms, Squamous Cell/genetics,metabolism,virology Nuclear Proteins/biosynthesis,genetics,immunology Oncogene Proteins, Viral/biosynthesis,genetics Papillomavirus E7 Proteins Papillomavirus Infections/genetics,metabolism,virology Protein Isoforms/biosynthesis,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,metabolism,virology Vulvar Diseases/genetics,metabolism Vulvar Neoplasms/genetics,metabolism,virology
Chemicals
Cyclin-Dependent Kinase Inhibitor p16 DNA-Binding Proteins Nuclear Proteins Oncogene Proteins, Viral Papillomavirus E7 Proteins Protein Isoforms RNA, Neoplasm TP73 protein, human Tumor Protein p73 Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53 Tumor Suppressor Proteins oncogene protein E7, Human papillomavirus type 16
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
O'Nions J
Ludwig Institute for Cancer Research, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG .
Brooks L A
Sullivan A
Bell A
Dunne B
Rozycka M
Reddy A
Tidy J A
Evans D
Farrell P J
Evans A
Gasco M
Gusterson B
Crook T
References (28)
28 references, click to expand
  1. Analysis of p73 in human borderline and invasive ovarian tumor.
    Oncogene. 2000 Apr 6;19(15):1885-90 PMID: 10773878
  2. New p73 variants with altered C-terminal structures have varied transcriptional activities.
    Oncogene. 1999 Sep 2;18(35):4993-8 PMID: 10490834
  3. p63 and p73 transactivate differentiation gene promoters in human keratinocytes.
    Biochem Biophys Res Commun. 2000 Jun 24;273(1):342-6 PMID: 10873608
  4. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation.
    Nature. 2000 Oct 5;407(6804):642-5 PMID: 11034214
  5. Role for the p53 homologue p73 in E2F-1-induced apoptosis.
    Nature. 2000 Oct 5;407(6804):645-8 PMID: 11034215
  6. Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus.
    Cancer Res. 2000 Dec 15;60(24):6875-7 PMID: 11156383
  7. Oncogenes induce and activate endogenous p73 protein.
    J Biol Chem. 2001 Apr 6;276(14):11310-6 PMID: 11115495
  8. Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53.
    Oncogene. 2001 Jan 25;20(4):514-22 PMID: 11313982
  9. Carcinoma of the vulva: epidemiology and pathogenesis.
    Obstet Gynecol. 1992 Mar;79(3):448-54 PMID: 1310806
  10. HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes.
    EMBO J. 1994 Feb 15;13(4):871-8 PMID: 8112300
  11. Carcinoma of the vulva: HPV and p53 mutations.
    Oncogene. 1994 Jun;9(6):1655-9 PMID: 8183560
  12. Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.
    Cancer Res. 1994 Oct 1;54(19):5050-3 PMID: 7923115
  13. Methylation of the 5' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing.
    Cancer Res. 1995 Oct 15;55(20):4531-5 PMID: 7553622
  14. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6 PMID: 8790415
  15. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.
    Cell. 1997 Aug 22;90(4):809-19 PMID: 9288759
  16. p73 is a simian [correction of human] p53-related protein that can induce apoptosis.
    Nature. 1997 Sep 11;389(6647):191-4 PMID: 9296498
  17. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2.
    EMBO J. 1998 Sep 1;17(17):5001-14 PMID: 9724636
  18. The human p19ARF protein encoded by the beta transcript of the p16INK4a gene is frequently lost in small cell lung cancer.
    Cancer Res. 1998 Sep 1;58(17):3926-31 PMID: 9731504
  19. p14ARF links the tumour suppressors RB and p53.
    Nature. 1998 Sep 10;395(6698):124-5 PMID: 9744267
  20. Two new p73 splice variants, gamma and delta, with different transcriptional activity.
    J Exp Med. 1998 Nov 2;188(9):1763-8 PMID: 9802988
  21. Allelic loss in human papillomavirus-positive and -negative vulvar squamous cell carcinomas.
    Am J Pathol. 1999 Apr;154(4):1009-15 PMID: 10233839
  22. Mutational analysis of p73 and p53 in human cancer cell lines.
    Oncogene. 1999 Jun 3;18(22):3415-21 PMID: 10362363
  23. Elevated and biallelic expression of p73 is associated withprogression of human bladder cancer.
    Cancer Res. 1999 Jun 15;59(12):2791-3 PMID: 10383132
  24. Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma.
    J Natl Cancer Inst. 1999 Jul 7;91(13):1154-8 PMID: 10393724
  25. Overexpression of the wild type p73 gene in breast cancer tissues and cell lines.
    Cancer Res. 1999 Jul 1;59(13):3257-63 PMID: 10397274
  26. Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation.
    Cancer Res. 1999 Jul 15;59(14):3352-6 PMID: 10416592
  27. Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation.
    Blood. 1999 Aug 1;94(3):1113-20 PMID: 10419905
  28. A common polymorphism acts as an intragenic modifier of mutant p53 behaviour.
    Nat Genet. 2000 May;25(1):47-54 PMID: 10802655
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
2001-11-16
Pages
1551-6
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2363945
Subset
IM
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