In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

Breuksch, Ines; Welter, Jonas; Bauer, Horst; Enklaar, Thorsten; Frees, Sebastian; Thüroff, Joachim W.; Hasenburg, Annette; Prawitt, Dirk; Brenner, Walburgis

doi:10.1186/s12964-018-0247-9

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…51 In addition, it has been described a PTEN-Δ splice isoform, which lacks the PTEN residues 344-403 encoded in exon 9 as a result of incorporation of intron 8 into the PTEN mRNA. 37,38 Finally, PTEN can be cleaved by caspase-3 at residues Asp371, Asp375, and Asp384, generating catalytically-competent PTEN truncated forms with altered stability and subcellular localization, and with defective interaction with protein partners 44,53 (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

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Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology

et al. 2019

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Anti-PTEN monoclonal antibodies (mAb) are arising as important tools for immunohistochemistry (IHC) and protein quantification routine analysis in clinical oncology. Although an effort has been made to document the reliability of tumor tissue section immunostaining by anti-PTEN mAb, and to standardize their IHC use in research and in the clinical practice, the precise topological and biochemical definition of the epitope recognized by each mAb has been conventionally overlooked. In this study, six commercial anti-PTEN mAb have been validated and characterized for sensitivity and specificity by IHC and FISH, using a set of prostate and urothelial bladder tumor specimens, and by immunoblot, using PTEN positive and PTEN negative human cell lines. Immunoblot precise epitope mapping, performed using recombinant PTEN variants and mutations, revealed that all mAb recognized linear epitopes of 6–11 amino acid length at the PTEN C-terminus. Tumor-associated or disease-associated mutations at the PTEN C-terminus did not affect subcellular localization or PIP3 phosphatase activity of PTEN in cells, although resulted in specific loss of reactivity for some mAb. Furthermore, specific mimicking-phosphorylation mutations at the PTEN C-terminal region also abolished binding of specific mAb. Our study adds new evidence on the relevance of a precise epitope mapping in the validation of anti-PTEN mAb for their use in the clinics. This will be substantial to provide a more accurate diagnosis in clinical oncology based on PTEN protein expression in tumors and biological fluids.

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Section: Discussionmentioning

confidence: 99%

“…33–35 In addition, several PTEN splice variants have been identified, 36,37 among which PTEN-Δ, lacking the C-terminal PTEN residues encoded in exon 9, has been proposed to have similar function as PTEN. 38…”

Section: Introductionmentioning

confidence: 99%

Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology

et al. 2019

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“…Chen, Chen, He, & Stiles, 2018). The studies displayed that PTEN was downregulated in KC (C. Zhu, Wei, Tian, Li, & Li, 2015) and could exert an antitumor role (Breuksch et al, 2018). Further study had demonstrated that PTEN can be a marker for KC (Rieken et al, 2017).…”

mentioning

confidence: 99%

Retracted: Circular RNA circC3P1 restrains kidney cancer cell activity by regulating miR‐21/PTEN axis and inactivating PI3K/AKT and NF‐kB pathways

Chen

Xin

et al. 2019

Journal Cellular Physiology

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Kidney cancer (KC) seriously impacts public health. We detected the function and mechanism of circular RNA C3P1 (circC3P1) in KC cells. CCK-8, flow cytometry, migration, and invasion assay were respectively used to investigate the efficacies of circC3P1 and microRNA (miR)-21 on cell viability, apoptosis, migration, and invasion.Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), circC3P1, and miR-21 expression were changed by cell transfection and detected by quantitative reverse-transcription polymerase chain reaction. Moreover, the apoptosis/pathways-related proteins and proteins were detected by western blot analysis.Besides, the relation between PTEN and miR-21 was detected by luciferase assay. circC3P1 and PTEN were downregulated while miR-21 was upregulated in KC tissues. circC3P1 declined cell viability, migration, and invasion and caused apoptosis. Furthermore, circC3P1 negatively regulated miR-21; miR-21 mimic could reverse the efficacies of circC3P1. Besides, circC3P1 restrained the PI3K/AKT and NF-κB pathways by downregulating miR-21. Finally, PTEN was authenticated as a target of miR-21. circC3P1 restrained KC cell growth, migration, and invasion by regulating miR-21/PTEN axis and inactivating PI3K/AKT and NF-κB signaling pathways.

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“…There are several variants of PTEN , including a variant containing intron 8 ( PTEN δ ) (Sharrard and Maitland, 2000 ). The function of PTEN δ is reported to be similar to that of PTEN (Breuksch et al , 2018 ), but the details are unknown. We analyzed the expression level and nucleotide sequence of PTEN δ by RT-qPCR and Sanger sequencing using the primers designed for exon 7 and intron 8.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells

Obayashi

Hamada

Yamasaki

et al. 2022

In Vitro Cell.Dev.Biol.-Animal

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Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by multiple hamartomas in various organs such as the mucosa, skin, and gastrointestinal tract. Patients with CS are at high risk for breast and thyroid cancers. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that negatively regulates the AKT pathway, and PTEN mutations are known to be the major causes of this syndrome. However, the pathogenesis of this syndrome has not been clarified. Here, we present a case of a Japanese woman with multiple oral polyps, breast cancer, and thyroid cancer who was clinically diagnosed with CS. We obtained DNA and RNA samples from the patient’s peripheral blood mononuclear cells (PBMCs) and buccal mucosa tumor. Next-generation sequencing revealed novel germline mutations (c.1020delT and c.1026G > A) in exon 8 of PTEN. Sanger sequencing identified no PTEN transcript from the mutant allele. Furthermore, CS-specific induced pluripotent stem cells (CS-iPSCs) were established from PBMCs of the patient under feeder- and serum-free culture. Compared with healthy PBMCs and iPSCs, both of the CS-derived PBMCs and CS-iPSCs exhibited significantly reduced expression of the PTEN transcript. The transcriptional variant, PTENδ, was increased in CS-iPSCs, suggesting that it may be the cause of the disease.

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In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

Cited by 18 publications

References 38 publications

Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology

Precise definition of PTEN C-terminal epitopes and its implications in clinical oncology

Retracted: Circular RNA circC3P1 restrains kidney cancer cell activity by regulating miR‐21/PTEN axis and inactivating PI3K/AKT and NF‐kB pathways

Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells

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