We are analyzing https://link.springer.com/article/10.1186/s13046-018-0744-0.

Title:
GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2 | Journal of Experimental & Clinical Cancer Research
Description:
Background Growth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily, and evidence suggests that a substantial amount of GDF15 is secreted in various human cancers, such as ovarian cancer, prostate cancer, and breast cancer, among others. However, the function of GDF15 in cervical cancer has not yet been reported. Methods Immunohistochemistry was used to detect GDF15 expression in normal cervix and in different cervical cancer lesions. Cell growth curves, MTT, tumor formation assays and flow cytometry were utilized to observe the effects of ectopic GDF15 expression on the proliferation and cell cycle of cervical cancer cells. Real-time PCR, western blotting and immunoprecipitation assays were conducted to measure the expression of genes related to the cell cycle and the PI3K/AKT and MAPK/ERK signaling pathways. A chromatin immunoprecipitation assay was performed to confirm whether C-myc bound to a specific region of the GDF15 promoter. Inhibitor treatment and immunoprecipitation assays were employed to identify the association between GDF15 and ErbB2. Results GDF15 expression gradually increased during the progression of cervical carcinogenesis. GDF15 promoted cervical cancer cell proliferation via exogenous rhGDF15 treatment or the use of gene editing technology in vitro and in vivo and significantly accelerated the cell cycle transition from G0/G1 to S phase. The expression of p-ErbB2, p-AKT1, p-Erk1/2, CyclinD1 and CyclinE1 was up-regulated and the expression of p21 was down-regulated in GDF15-overexpressing and rhGDF15-treated cervical cancer cells. C-myc trans-activated GDF15 expression by binding to the E-box motifs in the promoter of GDF15 and contributed to the positive feedback of GDF15/C-myc/GDF15. Furthermore, GDF15 bound to ErbB2 in a protein complex in cervical cancer cells. Conclusions Our data demonstrated that GDF15 promoted the proliferation of cervical cancer cells via the up-regulation of CyclinD1 and CyclinE1 and the down-regulation of p21 through both the PI3K/AKT and MAPK/ERK signaling pathways in a complex with ErbB2.
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Keywords {🔍}

gdf, cells, cancer, cell, cervical, expression, pubmed, article, proliferation, google, scholar, fig, human, siha, hela, shown, cycle, cas, cmyc, data, erbb, usa, growth, control, western, blotting, helagdf, sihagdf, analysis, factor, tumor, pathways, inhibitor, study, akt, pikakt, foxo, assay, samples, erk, rhgdf, phase, protein, additional, central, signaling, pakt, perk, carcinoma, file,

Topics {✒️}

px330-u6-chimeric_bb-cbh-hspcas9 plasmid wnt/beta-catenin signaling pathway peng-sheng zheng mapk/erk signaling-related proteins transforming growth factor-beta akt/mapk signaling-related proteins trans-suppression akt1/p-akt1 expression balb/c-nude mice showed wnt/beta-catenin pathway pearson linear-regression analysis tgf-beta receptor ii medical-ethics approval practices article download pdf 167-amino-acid pro-peptide mapk/erk signaling pathways 29-amino-acid signal peptide cell cycle-related genes 112-amino-acid mature protein empty pires2-acgfp vector predicts unfavorable prognosis 20 mg/ml propidium iodide tgf-β receptor inhibitor real time-pcr assays macrophage inhibitory cytokine-1 mechanism-based cancer therapeutics tgf-βr inhibitor treatment determine immuno-reactivity scores ez-chip assay kit crispr/cas systems quantitative real time-pcr real time-pcr experiments pires2-acgfp-gdf15 vector gdf15-overexpressing cervical cells foxo transcription factor ras-gtp significantly increased gdf15-overexpressing cells formed related subjects relative positive-staining area gdf15-modified cervical cells squamous intraepithelial lesions cell growth curves immuno-histochemical staining results privacy choices/manage cookies enhanced cell proliferation pi3k/akt/foxo pathway squamous cervical cancer full access ping zhang prostate-derived factor tgf-βr inhibitor

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         headline:GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2
         description:Growth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily, and evidence suggests that a substantial amount of GDF15 is secreted in various human cancers, such as ovarian cancer, prostate cancer, and breast cancer, among others. However, the function of GDF15 in cervical cancer has not yet been reported. Immunohistochemistry was used to detect GDF15 expression in normal cervix and in different cervical cancer lesions. Cell growth curves, MTT, tumor formation assays and flow cytometry were utilized to observe the effects of ectopic GDF15 expression on the proliferation and cell cycle of cervical cancer cells. Real-time PCR, western blotting and immunoprecipitation assays were conducted to measure the expression of genes related to the cell cycle and the PI3K/AKT and MAPK/ERK signaling pathways. A chromatin immunoprecipitation assay was performed to confirm whether C-myc bound to a specific region of the GDF15 promoter. Inhibitor treatment and immunoprecipitation assays were employed to identify the association between GDF15 and ErbB2. GDF15 expression gradually increased during the progression of cervical carcinogenesis. GDF15 promoted cervical cancer cell proliferation via exogenous rhGDF15 treatment or the use of gene editing technology in vitro and in vivo and significantly accelerated the cell cycle transition from G0/G1 to S phase. The expression of p-ErbB2, p-AKT1, p-Erk1/2, CyclinD1 and CyclinE1 was up-regulated and the expression of p21 was down-regulated in GDF15-overexpressing and rhGDF15-treated cervical cancer cells. C-myc trans-activated GDF15 expression by binding to the E-box motifs in the promoter of GDF15 and contributed to the positive feedback of GDF15/C-myc/GDF15. Furthermore, GDF15 bound to ErbB2 in a protein complex in cervical cancer cells. Our data demonstrated that GDF15 promoted the proliferation of cervical cancer cells via the up-regulation of CyclinD1 and CyclinE1 and the down-regulation of p21 through both the PI3K/AKT and MAPK/ERK signaling pathways in a complex with ErbB2.
         datePublished:2018-04-10T00:00:00Z
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            Proliferation
            ErbB2
            Cervical cancer
            Cancer Research
            Immunology
            Apoptosis
            Oncology
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      headline:GDF15 promotes the proliferation of cervical cancer cells by phosphorylating AKT1 and Erk1/2 through the receptor ErbB2
      description:Growth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily, and evidence suggests that a substantial amount of GDF15 is secreted in various human cancers, such as ovarian cancer, prostate cancer, and breast cancer, among others. However, the function of GDF15 in cervical cancer has not yet been reported. Immunohistochemistry was used to detect GDF15 expression in normal cervix and in different cervical cancer lesions. Cell growth curves, MTT, tumor formation assays and flow cytometry were utilized to observe the effects of ectopic GDF15 expression on the proliferation and cell cycle of cervical cancer cells. Real-time PCR, western blotting and immunoprecipitation assays were conducted to measure the expression of genes related to the cell cycle and the PI3K/AKT and MAPK/ERK signaling pathways. A chromatin immunoprecipitation assay was performed to confirm whether C-myc bound to a specific region of the GDF15 promoter. Inhibitor treatment and immunoprecipitation assays were employed to identify the association between GDF15 and ErbB2. GDF15 expression gradually increased during the progression of cervical carcinogenesis. GDF15 promoted cervical cancer cell proliferation via exogenous rhGDF15 treatment or the use of gene editing technology in vitro and in vivo and significantly accelerated the cell cycle transition from G0/G1 to S phase. The expression of p-ErbB2, p-AKT1, p-Erk1/2, CyclinD1 and CyclinE1 was up-regulated and the expression of p21 was down-regulated in GDF15-overexpressing and rhGDF15-treated cervical cancer cells. C-myc trans-activated GDF15 expression by binding to the E-box motifs in the promoter of GDF15 and contributed to the positive feedback of GDF15/C-myc/GDF15. Furthermore, GDF15 bound to ErbB2 in a protein complex in cervical cancer cells. Our data demonstrated that GDF15 promoted the proliferation of cervical cancer cells via the up-regulation of CyclinD1 and CyclinE1 and the down-regulation of p21 through both the PI3K/AKT and MAPK/ERK signaling pathways in a complex with ErbB2.
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         Proliferation
         ErbB2
         Cervical cancer
         Cancer Research
         Immunology
         Apoptosis
         Oncology
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      name:Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People’s Republic of China, Xi’an, People’s Republic of China
      name:Department of Reproductive Medicine, the First Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, People’s Republic of China

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