| 1. |
- Kurtsdotter, Idha, et al.
(författare)
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SOX5/6/21 prevent oncogene-driven transformation of brain stem cells
- 2017
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:18, s. 4985-4997
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult.
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| 2. |
- Ma, Yuanjun, et al.
(författare)
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Identification of mutations, gene expression changes and fusion transcripts by whole transcriptome RNAseq in docetaxel resistant prostate cancer cells
- 2016
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Docetaxel has been the standard first-line therapy in metastatic castration resistant prostate cancer. The survival benefit is, however, limited by either primary or acquired resistance. In this study, Du145 prostate cancer cells were converted to docetaxel-resistant cells Du145-R and Du145-RB by in vitro culturing. Next generation RNAseq was employed to analyze these cell lines. Forty-two genes were identified to have acquired mutations after the resistance development, of which thirty-four were found to have mutations in published sequencing studies using prostate cancer samples from patients. Fourteen novel and 2 previously known fusion genes were inferred from the RNA-seq data, and 13 of these were validated by RT-PCR and/or re-sequencing. Four in-frame fusion transcripts could be transcribed into fusion proteins in stably transfected HEK293 cells, including MYH9-EIF3D and LDLR-RPL31P11, which were specific identified or up-regulated in the docetaxel resistant DU145 cells. A panel of 615 gene transcripts was identified to have significantly changed expression profile in the docetaxel resistant cells. These transcriptional changes have potential for further study as predictive biomarkers and as targets of docetaxel treatment.
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| 3. |
- Peng, Zhuochun, et al.
(författare)
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Improving the Prediction of Prostate Cancer Overall Survival by Supplementing Readily Available Clinical Data with Gene Expression Levels of IGFBP3 and F3 in Formalin-Fixed Paraffin Embedded Core Needle Biopsy Material
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background A previously reported expression signature of three genes (IGFBP3, F3 and VGLL3) was shown to have potential prognostic value in estimating overall and cancer-specific survivals at diagnosis of prostate cancer in a pilot cohort study using freshly frozen Fine Needle Aspiration (FNA) samples. Methods We carried out a new cohort study with 241 prostate cancer patients diagnosed from 20042007 with a follow-up exceeding 6 years in order to verify the prognostic value of gene expression signature in formalin fixed paraffin embedded (FFPE) prostate core needle biopsy tissue samples. The cohort consisted of four patient groups with different survival times and death causes. A four multiplex one-step RT-qPCR test kit, designed and optimized for measuring the expression signature in FFPE core needle biopsy samples, was used. In archive FFPE biopsy samples the expression differences of two genes (IGFBP3 and F3) were measured. The survival time predictions using the current clinical parameters only, such as age at diagnosis, Gleason score, PSA value and tumor stage, and clinical parameters supplemented with the expression levels of IGFBP3 and F3, were compared. Results When combined with currently used clinical parameters, the gene expression levels of IGFBP3 and F3 are improving the prediction of survival time as compared to using clinical parameters alone. Conclusion The assessment of IGFBP3 and F3 gene expression levels in FFPE prostate cancer tissue would provide an improved survival prediction for prostate cancer patients at the time of diagnosis.
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