A Specific Role for AKT3 in the Genesis of Ovarian Cancer through Modulation of G2-M Phase Transition

Cristiano, Briony E.; Chan, Joanna C.; Hannan, Katherine M.; Lundie, Nicole A; Marmy-Conus, Nelly; Campbell, Ian; Phillips, Wayne A.; Robbie, Melissa; Hannan, Ross D.; Pearson, Richard B.

doi:10.1158/0008-5472.can-06-1968

Cited by 90 publications

(90 citation statements)

References 45 publications

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“…Dysregulation of putative target genes within these lists have been described in ovarian cancer. [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] E-cadherin and acatenin, components of the cadherin pathway, have previously been found to be dysregulated in metatstatic ovarian carcinoma and serous effusions. [79][80][81] Polymorphisms in cyclin D2 and protein kinase C isoform expression have been linked with prognosis in ovarian carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…87,88 AKT3, a component of the T-cell activation pathway, has been found to be highly expressed in a subset of ovarian serous carcinomas, and has been implicated as a key mediator of ovarian oncogenesis by the PI3K/AKT pathway. 78 PIK3R1, part of the same family of lipid kinases has also been implicated as an oncogene in ovarian tumourigenesis. 86 These putative targets indicate that miR-195 and miR-497 may have multiple biological roles in primary peritoneal carcinoma tumourigenesis.…”

Section: Discussionmentioning

confidence: 99%

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Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. We characterized the alteration in expression of a select group of microRNAs in primary peritoneal carcinoma relative to matched cases of ovarian serous carcinoma. MicroRNA expression was analysed using semi-quantitative stem-loop RT-PCR on a set of 34 formalin-fixed paraffin-embedded samples. Protein expression of p53 and bcl-2 was quantified in the corresponding tissue microarray. We provide definitive evidence that there is downregulation of a select group of microRNAs in tumours meeting Gynaecological Oncology Group criteria for primary peritoneal carcinoma relative to ovarian serous carcinoma. Specifically, we show decreased p53 expression and downregulation of miR-195 and miR-497 from the microRNA cluster site at chromosome 17p13.1 in primary peritoneal carcinoma relative to ovarian serous carcinoma. miR-195 and miR-497 may have potential roles as tumour-suppressor genes in primary peritoneal tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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“…AKT mediates survival signals that protect cells from apoptosis and is a potentially important therapeutic target. AKT3 levels in various ovarian cancer cell lines correlate with total AKT activity and proliferation rates, suggesting an important role in the genesis of at least one subset of ovarian cancer (Cristiano et al, 2006). Altomare et al (2004) suggested that low AKT activity is associated with chemotherapy resistance in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of epithelial ovarian cancer reveals key genes and pathways associated with chemotherapy resistance

Zhang

Luo

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study is to analyze gene expression data to identify key genes and pathways associated with resistance to platinumbased chemotherapy in epithelial ovarian cancer (EOC) and to improve clinical treatment strategies. The gene expression data set was downloaded from Gene Expression Omnibus and included 12 chemotherapy-resistant EOC samples and 16 chemotherapy-sensitive EOC samples. A differential analysis was performed to screen out differentially expressed genes (DEGs). A functional enrichment analysis was conducted for the DEGs using the database for annotation, visualization, and integration discovery. A protein-protein interaction (PPI) network was constructed with information from the human protein reference database. Pathway-pathway interactions were determined with a test based on the hypergeometric distribution. A total of 1564 DEGs were identified in chemotherapy-sensitive EOC, including 654 upregulated genes and 910 downregulated genes. The top three upregulated genes were HIST1H3G, AKT3, and RTN3, while the top three downregulated genes were NBLA00301, TRIM62, and EPHA5. A Gene Ontology enrichment analysis showed that cell adhesion, biological adhesion, and intracellular signaling cascades were significantly enriched in the DEGs. A KEGG pathway enrichment analysis revealed that the calcium, mitogen-activated protein kinase, and B cell receptor signaling pathways were significantly over-represented in the DEGs. A PPI network containing 101 interactions was acquired. The top three hub genes were RAC1, CAV1, and BCL2. Five modules were identified from the PPI network. Taken together, these findings could advance the understanding of the molecular mechanisms underlying intrinsic chemotherapy resistance in EOC.

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“…Cristiano et al (106) reported upregulation of Akt3 in 20% of ovarian tumors. Their data showed that ablation of Akt3 with shRNA resulted in decreased proliferation of ovarian tumor cells by arresting cell cycle progression at G2/M (106).…”

Section: Akt3 Deregulation In Other Types Of Cancermentioning

confidence: 99%

The Akt isoforms, their unique functions and potential as anticancer therapeutic targets

Santi¹,

Douglas²,

Lee³

2010

BioMolecular Concepts

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Akt (also known as protein kinase B or PKB) is the major downstream nodal point of the PI3K signaling pathway. This pathway is a promising anticancer therapeutic target, because constitutive activation of the PI3K-Akt pathway is correlated with tumor development, progression, poor prognosis, and resistance to cancer therapies. The Akt serine/threonine kinase regulates diverse cellular functions including cell growth, proliferation, glucose metabolism, and survival. Although all three known Akt isoforms (Akt1-3) are encoded by separate genes, their amino acid sequences show a high degree of similarity. For this and other reasons, it has long been assumed that all three Akt isoforms are activated in the same way, and their functions largely overlap. However, accumulating lines of evidence now suggest that the three Akt isoforms might have unique modes of activation and many distinct functions. In particular, it has recently been found that the Akt isoforms are localized at different subcellular compartments in both adipocytes and cancer cells. In this review, we highlight the unique roles of each Akt isoform by introducing published data obtained from both in vitro and in vivo studies. We also discuss the significant potential of the Akt isoforms as effective anticancer therapeutic targets.

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A Specific Role for AKT3 in the Genesis of Ovarian Cancer through Modulation of G2-M Phase Transition

Cited by 90 publications

References 45 publications

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

Gene expression profiling of epithelial ovarian cancer reveals key genes and pathways associated with chemotherapy resistance

The Akt isoforms, their unique functions and potential as anticancer therapeutic targets

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