title: Overexpression and ratio disruption of ΔNp63 and TAp63 isoform equilibrium in endometrial adenocarcinoma: correlation with obesity, menopause, and grade I/II tumors.
abstract: OBJECTIVE
  p63 plays an important role in several intracellular processes such as transcription activation and apoptosis. p63 has two N-terminal isoforms, TAp63 and ΔNp63. TAp63 isoform has p53-like functions, while ΔNp63 acts as a dominant negative inhibitor of the p53 family and is considered oncogenic. Although p63 and its isoforms are overexpressed in a wide variety of human malignancies such as cervical, head and neck, and lung cancer, their role in endometrial carcinoma has not been investigated.
  
  
  METHODS
  We measured by quantitative real-time polymerase chain reaction the mRNA expression of TAp63 and ΔNp63 in a series of 20 endometrioid adenocarcinomas paired with adjacent normal tissue.
  
  
  RESULTS
  TAp63 isoform exhibited 1.8-fold overexpression in malignant samples, while ΔNp63 was 4.3-fold overexpressed in cancer specimens. Further analysis revealed that the ΔN/TA isoform ratio shifted from 0.5 in normal samples to 1.2 in tumor specimens. Statistical analysis also revealed an association of TAp63 expression with high body mass index (p = 0.034), late menopause (p = 0.020), and lower tumor grade (p = 0.034). ΔNp63 was also correlated with grade I/II tumors (p = 0.044).
  
  
  CONCLUSIONS
  These results indicate that both p63 isoforms and especially ΔNp63 play an important role in the development and progression of grade I/II endometrial adenocarcinoma, especially in obese and late-menopause women.
authors.affiliation: Laboratory of Clinical Virology, Medical School, University of Crete, PO Box 2208, Heraklion, 71003 Crete, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Vakonaki
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Soulitzis
authors.forename: Stavros
authors.initials: S
authors.lastname: Sifakis
authors.forename: Danae
authors.initials: D
authors.lastname: Papadogianni
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutroulakis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D060787:Neoplasm Grading; D009765:Obesity / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins