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Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs

Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measu...

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Autores principales: Yao, Xiaohui, Liu, Qian, Zhao, Sida, Cheng, Rui, Liu, Chunhui, Zhang, Gangli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963423/
https://www.ncbi.nlm.nih.gov/pubmed/36837574
http://dx.doi.org/10.3390/medicina59020373
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author Yao, Xiaohui
Liu, Qian
Zhao, Sida
Cheng, Rui
Liu, Chunhui
Zhang, Gangli
author_facet Yao, Xiaohui
Liu, Qian
Zhao, Sida
Cheng, Rui
Liu, Chunhui
Zhang, Gangli
author_sort Yao, Xiaohui
collection PubMed
description Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients’ combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients’ combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 ± 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients.
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spelling pubmed-99634232023-02-26 Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs Yao, Xiaohui Liu, Qian Zhao, Sida Cheng, Rui Liu, Chunhui Zhang, Gangli Medicina (Kaunas) Article Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients’ combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients’ combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 ± 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients. MDPI 2023-02-15 /pmc/articles/PMC9963423/ /pubmed/36837574 http://dx.doi.org/10.3390/medicina59020373 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yao, Xiaohui
Liu, Qian
Zhao, Sida
Cheng, Rui
Liu, Chunhui
Zhang, Gangli
Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title_full Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title_fullStr Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title_full_unstemmed Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title_short Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs
title_sort expression and clinical significance of mdm2 in non-functioning pitnets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963423/
https://www.ncbi.nlm.nih.gov/pubmed/36837574
http://dx.doi.org/10.3390/medicina59020373
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