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Title:
Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study | Tumor Biology
Description:
Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.
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pubmed, article, google, scholar, cancer, cas, cervical, ccafs, supplementary, expression, cells, fibroblasts, erα, human, tumor, estrogen, genes, receptor, cafs, central, early, cancerassociated, gene, late, cell, res, research, stage, bangalore, fig, alpha, india, progression, breast, department, institute, signaling, log, biology, role, study, kumar, cxca, stromal, microarray, access, carcinoma, jpeg, privacy, cookies,
Topics {✒️}
month download article/chapter akhilesh kumar bajpai & acharya late-stage c-cafs compared bone marrow-derived precursors cbp/p300 interacting protein nf-kappab-dependent manner v-ha-ras transfection akhilesh kumar bajpai fak-erk2 signaling pathway es/tools/venny/index orchestrate tumor-promoting inflammation late stage c-cafs late c-cafs compared real time pcr hpv-induced cervical lesions mpp treated c-cafs estrogen receptor alpha canonical er-α signaling shodhaka ls pvt hpv-negative cervical carcinomas study characterized c-cafs modulate c-caf function human papillomavirus-immortalized methyl piperidino pyrazole full article pdf luminal breast cancer erα target genes estrogen receptors α vivo cultured c-cafs uttam dungarmal bafna privacy choices/manage cookies squamous cell carcinoma estrogen receptor response human protein atlas polarized cell type computational biology solutions late stage disease progesterone receptor expression late stage cafs treated c-cafs breast tumor cells physiological level estrogen human c-cafs mpp treated cafs cafs expressed erα oestrogen receptor antagonist gene expression patterns late stage cxca article kumar human cervical cancer
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headline:Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study
description:Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.
datePublished:2015-10-24T00:00:00Z
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Cervical cancer
Cancer-Associated Fibroblasts
Estrogen Receptor Alpha
Estrogen Receptor antagonists
ICI 182,780
MPP-Methyl Piperidino Pyrazole
Cancer Research
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headline:Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study
description:Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.
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Cervical cancer
Cancer-Associated Fibroblasts
Estrogen Receptor Alpha
Estrogen Receptor antagonists
ICI 182,780
MPP-Methyl Piperidino Pyrazole
Cancer Research
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