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Tytuł pozycji:

CDK4/RB/E2Fs axis as potential therapeutic target of endometrial cancer.

Tytuł:
CDK4/RB/E2Fs axis as potential therapeutic target of endometrial cancer.
Autorzy:
Hu J; Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.
Shen J; Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. Electronic address: .
Sun J; Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China. Electronic address: .
Źródło:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2020 May; Vol. 125, pp. 109870. Date of Electronic Publication: 2020 Feb 04.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
MeSH Terms:
Biomarkers, Tumor*
Cyclin-Dependent Kinase 4/*metabolism
E2F Transcription Factors/*metabolism
Endometrial Neoplasms/*etiology
Endometrial Neoplasms/*metabolism
Retinoblastoma Protein/*metabolism
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cyclin-Dependent Kinase 4/genetics ; DNA Copy Number Variations ; Disease Models, Animal ; E2F Transcription Factors/genetics ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Molecular Targeted Therapy ; Mutation ; Prognosis ; Protein Binding ; Retinoblastoma Protein/genetics ; Signal Transduction/drug effects ; Transcriptional Activation ; Xenograft Model Antitumor Assays
Contributed Indexing:
Keywords: CDK4; Cell cycle; E2F1; E2F2; E2F3; Endometrial cancer
Substance Nomenclature:
0 (Antineoplastic Agents)
0 (Biomarkers, Tumor)
0 (E2F Transcription Factors)
0 (Retinoblastoma Protein)
EC 2.7.11.22 (CDK4 protein, human)
EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
Entry Date(s):
Date Created: 20200208 Date Completed: 20201214 Latest Revision: 20201214
Update Code:
20240105
DOI:
10.1016/j.biopha.2020.109870
PMID:
32032891
Czasopismo naukowe
The increasing incidence rate and decreasing patients' five-year survival rate for endometrial cancer (EC) in recent decades highlight the necessity for further investigation of the molecular characteristics involved in cancer initiation and progression. In this study, we found that the pathways associated with mitotic cell cycle were enriched in primary EC samples versus normal endometrial samples through analyzing RNA-seq data of The Cancer Genome Atlas (TCGA). The messenger RNA (mRNA) expression of three activator E2Fs (E2F1, E2F2, and E2F3) and their target genes increased significantly in EC samples. Additionally, the high transcriptional activity of activator E2Fs was associated with poor survival, advanced clinical stage, high histologic grade, and aggressive histological type. We further demonstrated that E2Fs hyperactivation correlated with DNA hypomethylation and high cyclin-dependent kinase 4 (CDK4) expression. Moreover, abemaciclib, a selective CDK4 inhibitor, significantly inhibited the proliferation rates of human EC cell lines in vitro. And, abemaciclib also obviously inhibited EC cell growth in nude mice model. Collectively, our data suggest that the misregulation of CDK4/RB/E2Fs axis is associated with EC oncogenesis, and abemaciclib is a potential targeted drug for EC.
Competing Interests: Declaration of Competing Interest All authors declare that they have no relevant conflicts of interest to disclose.
(Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

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