P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

Jiang, Zhongyong; Xu, Wei; Dan, Gang; Liu, Yuan; Xiong, Jie

doi:10.12659/msm.898616

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…The findings in the literature regarding the loss PTEN protein expression and clinical outcome in endometrial carcinomas are inconsistent. Some studies have reported more favorable survival (14,28,29,91,95,96), while other studies have indicated less favorable prognosis (19,90,97,98). Terakawa et al (97) suggested that overexpression of PTEN is a significant prognostic indicator of improved overall survival for patients with advanced endometrial carcinoma who undergo postoperative chemotherapy, as PTEN was able to increase the chemosensitivity of neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

“…Mdm2 also serves an oncogene role independent of p53. Notably, mdm2 overexpression leads to excessive cell proliferation and promotes tumor formation (29). Inactivation of p53 protein provides the neoplastic cells with a higher capacity for division and proliferation, and therefore contributes to malignant change and tumor formation (17,30).…”

Section: Introductionmentioning

confidence: 99%

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Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

et al. 2019

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Endometrial carcinoma is a common malignancy of the female genital tract. Alterations in the expression levels of various oncogenes and tumor suppressor genes serve important roles in the carcinogenesis and biological behavior of endometrial carcinoma. The aim of the present study was to evaluate the combination and individual expression of p53 and phosphatase and tensin homolog (PTEN) protein in human endometrial carcinoma. In addition, the correlation of these proteins with clinicopathological parameters was also assessed. Retrospective immunohistochemical analysis of the expression of p53 and PTEN tumor suppressor proteins was conducted in 99 women with endometrial carcinoma. The overall rate of p53 and PTEN positivity was 89 and 77%, respectively, according to the sum of stain intensity and scores of immunopositive cells. The sum of p53 positivity correlated strongly with PTEN expression (ρ=0.256; P=0.044). The concomitant sum of p53 and PTEN expression was identified in 45% of patients with endometrial adenocarcinoma. Notably, the sum of the immunohistochemical expression of p53 was significantly correlated with patient age (P=0.037), histologic type (P=0.008), histologic grade (P=0.002) and fallopian and/or ovarian invasion (P=0.014). Furthermore, PTEN expression was associated with myometrial invasion (ρ=−0.377; P=0.002) and clinical stage (P=0.019). In addition, concomitant p53 and PTEN expression was correlated with patient age (P=0.008) and histologic differentiation (P=0.028). The findings indicated a correlation between the expression of p53 and PTEN in endometrial adenocarcinoma, which suggested an intrinsic association between expression levels of these tumor suppressor genes. The study also suggested that concomitant p53 and PTEN expression contributed in characterizing the tumor behavior of endometrial carcinoma. Taken together, the present study suggested the combined expression of p53 and PTEN in the development of high-grade endometrial carcinoma in older patients. In addition, the findings indicated activation of different molecular pathways in the tumor progression between low-grade and high-grade endometrial carcinomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

et al. 2019

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“…MDM2 is an oncogene that promotes tumour occurrence and development predominantly by inhibiting the p53 tumour suppressor activity (24). Jiang et al (31) found increased MDM2 mRNA and protein levels with increasing EC grade.…”

Section: Discussionmentioning

confidence: 99%

Restoration of microRNA‑29c in type I endometrioid cancer reduced endometrial cancer cell growth

et al. 2019

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Endometrial cancer is the most common gynaecological cancer worldwide, and the prognosis of patients with advanced disease remains poor. MicroRNAs (miRs) are dysregulated in endometrial cancer. miRs-29-a, -b and -c expression levels are downregulated in endometrial cancer; however, a specific role for miR-29c and its target genes remain to be elucidated. The aim of the present study was to determine the functional effect of restoring miR-29c expression in endometrial cancer cell lines and to identify miR-29c targets involved in cancer progression. miR-29c expression in human endometrial tumour grades 1-3 and benign tissue as well as in the endometrial cancer cell lines Ishikawa, HEC1A and AN3CA were analysed using reverse transcriptase-quantitative PCR (RT-qPCR). The cell lines were transfected with miR-29c mimic, miR-29c inhibitor or scrambled control.xCELLigence real-time cell monitoring analysed proliferation and migration, and flow cytometry was used to analyse apoptosis and cell cycle. The expression of miR-29c target genes in transfected cell lines was analysed using RT-qPCR. miR-29c was downregulated in grade 1-3 endometrial cancer samples compared with benign endometrium. miR-29c was reduced in Ishikawa and AN3CA cells, but not in HEC1A cell lines compared with non-cancerous primary human endometrial epithelial cells. Overexpression of miR-29c variably reduced proliferation, increased apoptosis and reduced the expression levels of miR-29c target genes, including cell division cycle 42, HMG-box transcription factor 1, integrin subunit β 1, MCL1 apoptosis regulator BCL2 family member, MDM2 proto-oncogene, serum/glucocorticoid regulated kinase 1, sirtuin 1 and vascular endothelial growth factor A, across the three cell lines investigated. Inhibition of miR-29c in HEC1A cells increased proliferation and collagen type IV α 1 chain expression. The re-introduction of miR-29c to endometrial cancer cell lines reduced proliferation, increased apoptosis and reduced miR-29c target gene expression in vitro. The present results suggested that miR-29c may be a potential therapeutic target for endometrial cancer.

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“…El gen P53 es un gen supresor de tumor que juega un papel importante en la apoptosis celular y el gen MDM2 es un oncogen que puede estimular la proliferación celular del endometrio y otros tejidos. Un estudio realizado en China, donde se seleccionaron 71 muestras de diferentes lesiones endometriales de mujeres sometidas a histerectomía (adenocarcinoma, adenomiosis, poliposis y grupo control), y a las cuales se les realizó PCR en tiempo real para detectar la expresión de los genes P53 y MDM2, se encontró que dicha expresión fue significativamente más elevada en el grupo de adenocarcinoma, seguido por el grupo de pólipos y por último por el de adenomiosis, lo cual refleja que la aparición de pólipos endometriales puede promover la aparición y desarrollo del cáncer, y constituir una lesión preneoplásica; sin embargo hasta el momento no se cuenta con evidencia suficiente que permita establecer un protocolo de manejo de los pólipos endometriales para evitar así su malignización (15).…”

Section: Tratamientounclassified

Riesgo de malignización de pólipos endometriales

Salguero-Sánchez¹,

González-García²

2022

RSOGV

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Endometrial polyps are common lesions and their prevalence in the general population is relatively low; however, they can be associated with abnormal uterine bleeding, increased risk of endometrial cancer and, in some cases, infertility. These conditions can be considered as a malignant lesion depending on their characteristics. The risk of malignancy of an endometrial polyp varies between 0.8% to 8%. The malignancy that these represent cannot be observed in isolation but rather together with the other factors that increase the risk of endometrial cancer. The diagnosis is principally realized by transvaginal ultrasound and histeroscopia. The managing will depend on the individual evaluation of every patient and it can go from resection up to only follow-up. Keywords: Endometrial Polyps, Uterine Polyps, Endometrial Neoplasms, Risk factors, Polypectomy

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P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

Cited by 6 publications

References 21 publications

Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

Restoration of microRNA‑29c in type I endometrioid cancer reduced endometrial cancer cell growth

Riesgo de malignización de pólipos endometriales

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