ArticleOncogene2016
Akt regulates progesterone receptor B-dependent transcription and angiogenesis in endometrial cancer cells.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Obesity, Bariatric Surgery, and Cancer Risk: Nutritional Perspectives and Long-Term Clinical Implications.Nutrients · 2026Review
- CRL4International journal of biological sciences · 2026Article
- Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with AKT inhibition to suppress triple-negative breast cancer vascularization.Angiogenesis · 2025Article
- Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growthFrontiers in oncology · 2025Article
- AKT inhibitors in gynecologic oncology: past, present and future.Frontiers in oncology · 2025Review
- The Impact of High Adiposity on Endometrial Progesterone Response and Metallothionein Regulation.The Journal of clinical endocrinology and metabolism · 2024Article
- Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Effect of a protein kinase B (Akt) inhibitor on the angiogenesis of HUVECs and corneal neovascularization.Wiener klinische Wochenschrift · 2024Article
- Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Transcriptional response of endometrial cells to Insulin, cultured using microfluidics.Reproduction & fertility · 2023Article
- LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer.Frontiers in genetics · 2023Article
- Circular RNAs in endometrial carcinoma (Review).Oncology reports · 2022Review
- MIG-6 Is Critical for Progesterone Responsiveness in Human Complex Atypical Hyperplasia and Early-Stage Endometrial Cancer.International journal of molecular sciences · 2022Article
- Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer.Cancers · 2022Article
- Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients.Scientific reports · 2022Article
- Glucose transporters: Important regulators of endometrial cancer therapy sensitivity.Frontiers in oncology · 2022Review
- Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?Biomolecules · 2021Review
- Efficacy of the LNG-IUS for treatment of endometrial hyperplasia and early stage endometrial cancer: Can biomarkers predict response?Gynecologic oncology reports · 2021Review
- Chlorpromazine Sensitizes Progestin-Resistant Endometrial Cancer Cells to MPA by Upregulating PRB.Frontiers in oncology · 2021Article
- Characterization of Nuclear Progesterone Receptor Isoforms in the Term Equine Placenta.Frontiers in veterinary science · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Progestins have long been used clinically for the treatment of endometrial cancers; however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN-mutated endometrial cancers, hyperactive Akt signaling downregulates progesterone receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that inhibition of Akt with the Akt inhibitor, MK-2206 (MK), in conjunction with progestin (R5020) treatment, is sufficient to upregulate a subset of PRB target genes in Ishikawa cells stably expressing PRB (PRB-Ishikawa). Through gene ontology analysis of Akt-regulated PRB target genes, angiogenesis was found to be the principle process regulated by Akt-PRB. To further interrogate the mechanism by which Akt modulates PRB transcriptional activity, ChIP-Mass spectrometry was performed to identify potential cofactors that differentially interact with PRB in the presence of R5020 and MK+R5020. 14-3-3σ was identified as a protein enriched in the MK+R5020 data set, and it was demonstrated that 14-3-3σ is required for the upregulation in PRB target gene expression following inhibition of Akt. To determine the ramifications of MK+R5020 treatment on angiogenesis, in vitro assays were performed and combinatorial MK+R5020 treatment significantly decreased endothelial cell invasion and tube formation more than MK or R5020 treatment alone. Furthermore, we found that combinatorial MK-2206+progesterone treatments decreased angiogenesis and proliferation in the Pten(d/d) conditional mouse model of endometrial cancer. Taken together, these findings suggest that a combinatorial therapeutic approach utilizing Akt inhibitors with progestins may improve the efficacy of progestin therapy for the treatment of endometrial cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.