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Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells.

ABSTRACT: To understand the potential role of P2X(7) as biomarker of endometrial cancer, and the molecular mechanisms by which cancerous epithelial cells maintain low expression of P2X(7).Feasibility clinical experimental study. Normal (28), simple or complex hyperplasia (7), complex hyperplasia with atypia (6) and cancer endometrial discarded tissues (40) were obtained from a total of 81 women, ages 25-75. Endpoint for P2X(7) protein was average pixel signal density of tissue immunoreactivity with anti-P2X(7) antibody. Endpoint for P2X(7) mRNA was one-step quantitative Real-Time PCR. Experiments in-vitro included normal (hEVEC) and cancerous cervical epithelial cells (HeLa) transfected with reporter plasmid containing luciferase-3' untranslated region (3'UTR)-P2X(7) cDNA, using as endpoint steady-state luciferase mRNA levels.Levels of P2X(7) protein and mRNA were significantly lower in vivo, in tissues of complex hyperplasia with atypia or endometrial adenocarcinoma, than in tissues of normal endometrium, simple hyperplasia or complex hyperplasia tissues (sensitivity and specificity of 89-100%, p<0.0001-0.01). Steady-state levels of luciferase mRNA increased over a 6 h incubation period in hEVEC cells transfected with the 3'UTR-P2X(7)-luciferase vector, but decreased in HeLa cells transfected with the reporter plasmid.Tissue levels of P2X(7) protein and mRNA can differentiate effectively and accurately between normal and benign hyperplastic endometrial tissues from pre-cancerous and cancer tissues. Cancerous epithelial cells degrade P2X(7) mRNA by activation of instability domains located at the 3'UTR of the P2X(7).

SUBMITTER: Li X

PROVIDER: S-EPMC2398694 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells.

Li Xin X Qi Xiaoping X Zhou Lingyin L Catera Deborah D Rote Neal S NS Potashkin Judith J Abdul-Karim Fadi W FW Gorodeski George I GI

Gynecologic oncology 20070504 1

<h4>Objectives</h4>To understand the potential role of P2X(7) as biomarker of endometrial cancer, and the molecular mechanisms by which cancerous epithelial cells maintain low expression of P2X(7).<h4>Methods</h4>Feasibility clinical experimental study. Normal (28), simple or complex hyperplasia (7), complex hyperplasia with atypia (6) and cancer endometrial discarded tissues (40) were obtained from a total of 81 women, ages 25-75. Endpoint for P2X(7) protein was average pixel signal density of ...[more]

PMID: 17482244

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Project description:Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. The aim of this study was to analyze the expression of SNAIL, SLUG, TWIST1, TWIST2, ZEB1, and ZEB 2 in primary tumor and the correlation with morphological and clinical characteristics of EC. The study included 158 patients with EC after surgical treatments: total hysterectomy and lymphadenectomy. The percentages of EC specimens testing positively for the EMT transcription factors were 84.5% for SNAIL, 92.2% for SLUG, 10.9% for TWIST1, 100% for TWIST2, 89% for ZEB1, and 98% for ZEB2. The expression of SLUG in patients with FIGO stage III or IV, type II EC, myometrial invasion ? 50% of the uterine wall thickness, and adnexal involvement and in patients with distant metastases was significantly higher. SLUG and ZEB2 expressions were identified as significant predictors of higher FIGO stages (III or IV) on univariate analysis. The overexpression of SLUG was a significant predictor of more aggressive type II EC, myometrial?invasion ? 50% of the uterine wall thickness, and distant metastases on both univariate and multivariate analysis. Moreover, the overexpression of SLUG and ZEB2 was shown to be significant predictors of adnexal involvement on univariate analysis. ZEB 2 overexpression was identified in multivariate analysis as another independent predictor associated with a lesser likelihood of type II EC. Both univariate and multivariate analyses demonstrated that SLUG expression was the only predictor of 5-year survival in the study group. The overexpression of SLUG was associated with a significant increase in mortality hazard on univariate analysis and was shown to be a highly significant predictor of death on multivariate analysis. Conclusions. Selected proteins of the EMT pathway play a role in endometrial carcinogenesis; SLUG and ZEB2 expressions in the primary tumor might predict clinical outcomes in EC and drive therapeutic decisions regarding adjuvant treatment in patients with this malignancy.

Dataset Information

Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells.

Publications

Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells.

Similar Datasets

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