Prognostic value of cyclin B in endometrial endometrioid adenocarcinoma

Santala, Simi; Talvensaari-Mattila, Anne; Soini, Ylermi; Santala, Markku

doi:10.1007/s13277-014-2676-4

Cited by 10 publications

(10 citation statements)

References 25 publications

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“…S8F). Cyclin B1 upregulation has been previously observed to be associated with worse patient survival (33). Treatment with BETis reduced mRNA expression of Cyclin B1 in both Hec1-b and Ishikawa cells, with CPI203 producing a more significant decrease than CN210 (Supplementary Fig.…”

Section: Brd4 Directly Regulates Notch3 Expression and Impacts Notch3mentioning

confidence: 77%

Predicting Novel Therapies and Targets: Regulation of Notch3 by the Bromodomain Protein BRD4

Villar‐Prados

Court

et al. 2019

Molecular Cancer Therapeutics

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Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer.Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling.Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P < 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo. BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1. Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter.Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.

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Section: Brd4 Directly Regulates Notch3 Expression and Impacts Notch3mentioning

confidence: 77%

Predicting Novel Therapies and Targets: Regulation of Notch3 by the Bromodomain Protein BRD4

Villar‐Prados

Court

et al. 2019

Molecular Cancer Therapeutics

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“…Cyclins, a group of cell cycle regulatory proteins, were identified in the early 1980s as proteins that degraded at the end of each M phase cycle in sea urchin embryos (Santala et al, 2015). Subsequently, cyclins have been described in diverse organisms, from yeasts to humans (Li et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Catalytic activation of CDKs requires sufficient accumulation of cyclin protein at particular stages of the cell cycle (Pines and Hunter, 1990). Cyclin B is a protein kinase that is essential for G2/M phase transition and acts as an activator to CDK1 (Santala et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Characterization and expression analysis of a cyclin B gene from black tiger shrimp (Penaeus monodon)

Zhao¹,

Fu²,

Yang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The open reading frame of black tiger shrimp (Penaeus monodon) cyclin B (Pmcyclin B) was identified, based on cDNA sequence registered in GenBank (accession No. EF015590). The target sequence was 1206 bp, corresponding to 401 amino acids. Two conserved signature sequences of the cyclin B gene family were found in the Pmcyclin B deduced aa sequence. Temporal expression of Pmcyclin B in different tissues, including ovary, lymphoid organ, brain, blood, muscle, heart, gill, hepatopancreas, and intestine, were quantified by quantitative real time PCR. Messenger RNA expression levels of Pmcyclin B were greatest in the ovary, compared to other tissues (P < 0.05). Temporal expression of Pmcyclin B in the ovary at six different developmental stages was investigated by real-time PCR; no significant difference was observed (P < 0.05). Recombinant Pmcyclin B protein and its polyclonal antibody were (2015) successfully produced. Western blot analysis revealed differential expression of Pmcyclin B in ovaries in developmental stages II to IV; a positive signal (45 kDa) was observed in all ovarian stages assessed, but was most intense at stage III. Pmcyclin B protein was assessed by immunohistochemistry and was localized to the cytoplasm of prophase oocytes at stage II and enriched in the nuclei of pro-metaphase oocytes at stages III and IV. Results from this study indicate that Pmcyclin B is constitutively expressed and plays an important role in ovarian maturation in P. monodon.

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“…p27 positivity was evaluated as the percentage of positive nuclear staining/whole tumor area in the section. Other staining patterns were evaluated separately (8)(9)(10).…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we have analyzed the impact of cyclin A, cyclin B and cyclin E on endometrial endometrioid adenocarcinoma (8)(9). In this study, we evaluate the effects of p27 expression on conventional clinicopathological and prognostic factors in the same patient population and further analyze the correlations between cyclins A, B and E, as well as p27, and their relation to prognosis.…”

mentioning

confidence: 99%