ArticleCell communication and signaling : CCS2018
In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
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- The role of alternative pre-mRNA splicing in cancer progression.Cancer cell international · 2023Review
- Vasoactive intestinal peptide exerts therapeutic action by regulating PTEN in a model of Sjögren's disease.Immunity, inflammation and disease · 2023Article
- Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants.PloS one · 2023Article
- Research Progress of PI3K/PTEN/AKT Signaling Pathway Associated with Renal Cell Carcinoma.Disease markers · 2022Review
- Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells.In vitro cellular & developmental biology. Animal · 2022Article
- Retinoblastoma tumor cell proliferation is negatively associated with an immune gene expression signature and increased immune cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- The Complex Landscape ofCold Spring Harbor perspectives in medicine · 2020Review
- Knockdown of MAPK14 inhibits the proliferation and migration of clear cell renal cell carcinoma by downregulating the expression of CDC25B.Cancer medicine · 2020Observational
- Precise Immunodetection of PTEN Protein in Human Neoplasia.Cold Spring Harbor perspectives in medicine · 2019Review
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology.NPJ precision oncology · 2019Article
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9 authors at 2 institutions in 1 country.
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Abstract
backgroundLoss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression.
methodsIn specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro.
resultsPatients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown.
conclusionsWe could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.
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