Overexpression and ratio disruption of ΔNp63 and TAp63 isoform equilibrium in endometrial adenocarcinoma: correlation with obesity, menopause, and grade I/II tumors.

Abstract

PURPOSE:

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: Eleni Vakonaki, Nikolaos Soulitzis, Stavros Sifakis, Danae Papadogianni, Dimitrios Koutroulakis, Demetrios A Spandidos
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 8 Pg. 1271-8 (Aug 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22441934 (Publication Type: Journal Article)

Chemical References

• Protein Isoforms
• TP63 protein, human
• Transcription Factors
• Tumor Suppressor Proteins

Topics

• Adenocarcinoma (genetics, pathology)
• Adult
• Aged
• Aged, 80 and over
• Endometrial Neoplasms (genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Menopause
• Middle Aged
• Neoplasm Grading
• Obesity (pathology)
• Protein Isoforms (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Transcription Factors (genetics)
• Tumor Suppressor Proteins (genetics)
• Up-Regulation (genetics)