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

Vakonaki, E.; Soulitzis, Nikolaos; Sifakis, Stavros; Papadogianni, Danae; Koutroulakis, Dimitrios; Spandidos, Demetrios Α.

doi:10.1007/s00432-012-1200-8

Cited by 10 publications

(10 citation statements)

References 33 publications

(27 reference statements)

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“…[40,70] In addition, a recent report indicated that p63 plays important roles in the development and progression of grade I/II endometrial adenocarcinoma. [71] It has been suggested that dysregulated expression of p63 is often correlated with amplification of its genomic locus, 3q27-28 and is frequently occurred in human epithelial cancers. [40] Studies on a cohort of 245 esophageal tumors showed that both TAp63 and ΔNp63 isoforms were upregulated at the transcriptional level in squamous cell carcinoma.…”

Section: P63 In Cancersmentioning

confidence: 99%

Roles of p63 in Epidermal Development and Tumorigenesis

Yao¹,

Chen²

2012

Biomedical

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Epidermis is composed mainly of keratinocytes and is the ma-jor barrier of human body. The development and maintenance of normal epithelial structures and functions require the transcription factor p63. The p63 gene encodes proteins with structures similar to that of p53, including an N-terminal transactivation (TA) domain, a DNA-binding domain and a carboxy-oligomerization domain. TAp63 and ΔNp63 (p63 isoforms without TA domain) regulate a wide range of target genes that are important for embryonal development and epithelial integrity. Mutations of p63 gene cause epidermal abnormalities characterized by ectodermal dysplasia. Recent reports have indicated that p63 plays important role in tumorigenesis as well. However, the relative importance of TAp63 and ΔNp63 in epidermal development and tumorigenesis re-mains mostly unclear and awaits further investigation. In this review, we summarize the current knowledge on the structure and function of p63 and its isoforms.

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Section: P63 In Cancersmentioning

confidence: 99%

Roles of p63 in Epidermal Development and Tumorigenesis

Yao¹,

Chen²

2012

Biomedical

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“…From this result, we hypothesized whether not only the overexpression of ΔNp63, but also the imbalance of p63, is associated with cervical cancer carcinogenesis. Vakonaki et al reported that an imbalance of the ΔNp63 and TAp63 isoforms is associated with grade I/II tumors in endometrial adenocarcinoma in a study of 20 paired adjacent normal and cancer tissues [23]. Therefore, we investigated the imbalance of p63, defined as the ΔN/TAp63 mRNA expression ratio, in cervical cancer cell lines and tissues.…”

Section: Discussionmentioning

confidence: 99%

ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis

et al. 2019

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p63 is a transcription factor p53 family. Two major isoforms of p63, TAp63 with transactivation (TA) domain and ΔNp63 with truncated TA domain, have been reported to play opposing roles either in tumor suppression or oncogenic function. Little is known about the association of these two isoforms of p63 in the carcinogenesis of cervical cancer. In this study, the mRNA expression levels of TAp63 and ΔNp63 in 40 normal, 30 low-grade squamous intraepithelial lesions (LSIL), 38 high-grade squamous intraepithelial lesions (HSIL), and 52 cervical cancer formalin-fixed paraffin-embedded tissues were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). We analyzed the association between the ΔNp63 and ΔN/TAp63 mRNA expression ratio and clinicopathological parameters and compared disease-specific survival of each ΔNp63 mRNA expression and ΔN/TAp63 mRNA expression ratio. The ΔN/TAp63 mRNA expression ratio in cervical cancer showed higher sensitivity than the mRNA expression levels of ΔNp63 (52.0% vs 44.2%). The level of ΔN/TAp63 mRNA expression ratio in precancerous LSIL and HSIL was higher than in normal tissues ( P = 0.01 and P = 0.003) and lower than in cervical cancer tissues ( P = 0.03 and P = 0.02). Besides, the positive ΔN/TAp63 mRNA expression ratio was associated with bulky tumor size and high expression of Ki-67, the proliferation marker, in cervical cancer ( P = 0.04 and P = 0.02). The cervical cancer patients with the positive ΔN/TAp63 mRNA expression ratio showed worse survival compared to those who with the negative expression ratio of ΔN/TAp63 (HR = 5.7, 95% CI: 1.6–19.9). In conclusion, the balance of TAp63 and ΔNp63 is closely related to the carcinogenesis of cervical cancer. The ΔN/TAp63 mRNA expression ratio could be useful as a diagnostic and prognostic marker of cervical cancer.

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“…Furthermore, deletions, mutations and interactions with cellular or viral proteins have been recognized as key steps in the development of approximately half of all human cancers. Moreover, the TAp63 isoform had p53-like functions, whereas DNp63 functioned as a dominant negative inhibitor of the p53 family [18,19], which raises the question as to whether patients with TP63 mutations have an increased tumor incidence. However, there was no increased tumor incidence in our patients.…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Genes in EEC and LMS Syndromes

Song

Bian

2015

PLoS ONE

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ObjectivesEctrodactyly ectodermal dysplasia cleft lip/palate (EEC) syndrome and limb-mammary syndrome (LMS) share a similar phenotype and the same pathogenic gene, which complicates the ability to distinguish between these diagnoses. The current study aims to identify a potential and practical clinical biomarker to distinguish EEC from LMS.MethodsTwo EEC pedigrees and one LMS pedigree that have been previously reported were reanalyzed. After confirmation of the causative mutations for these new patients, whole-genome expression microarray analysis was performed to assess the molecular genetic changes in these families.ResultsFive new patients with classic symptoms were reported, and these individuals exhibited the same mutation as their relatives (c.812 G>C; c.611G>A; and c.680G>A). According to the whole genome expression results, the EEC patients exhibited different gene expression characteristics compared with the LMS patients. More than 5,000 genes were differentially expressed (changes >2 or <0.5-fold) among the EEC patients, LMS patients and healthy individuals. The top three altered pathways have been implicated in apoptosis, the hematopoietic cell lineage and the Toll-like receptor signaling pathway.ConclusionOur results provide additional clinical and molecular information regarding EEC and LMS and suggest that peripheral blood cytokines may represent a promising clinical biomarker for the diagnosis of these syndromes.

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

Abstract: 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.

Cited by 10 publications

References 33 publications

Roles of p63 in Epidermal Development and Tumorigenesis

Roles of p63 in Epidermal Development and Tumorigenesis

ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis

Differentially Expressed Genes in EEC and LMS Syndromes

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