Relationship between polycomb-group protein BMI-1 and phosphatases regulating AKT phosphorylation level in endometrial cancer.
Apoptosis
Biomarkers, Tumor
/ genetics
Case-Control Studies
Cell Proliferation
Endometrial Neoplasms
/ genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Neoplasm Invasiveness
Nuclear Proteins
/ genetics
PTEN Phosphohydrolase
/ genetics
Phosphoprotein Phosphatases
/ genetics
Phosphorylation
Polycomb Repressive Complex 1
/ genetics
Prognosis
Proto-Oncogene Proteins c-akt
/ genetics
Signal Transduction
Survival Rate
Tumor Cells, Cultured
AKT
BMI-1
PHLPP
PTEN
endometrial cancer
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
07
11
2018
revised:
24
08
2019
accepted:
29
08
2019
pubmed:
22
12
2019
medline:
11
5
2021
entrez:
22
12
2019
Statut:
ppublish
Résumé
The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.
Identifiants
pubmed: 31863623
doi: 10.1111/jcmm.14782
pmc: PMC6991679
doi:
Substances chimiques
BMI1 protein, human
0
Biomarkers, Tumor
0
Nuclear Proteins
0
Polycomb Repressive Complex 1
EC 2.3.2.27
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
PHLPP1 protein, human
EC 3.1.3.16
PHLPP2 protein, human
EC 3.1.3.16
Phosphoprotein Phosphatases
EC 3.1.3.16
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1300-1310Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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