TMPRSS2:ERG gene fusion expression regulates bone markers and enhances the osteoblastic phenotype of prostate cancer bone metastases
| Autor: | Rachel Deplus, Martine Duterque-Coquillaud, Anne Flourens, Edith Bonnelye, Nathalie Vanpouille, Tian V. Tian, Philippe Clézardin, Anais Fradet, Carine Delliaux, Xavier Leroy, Yvan de Launoit, Mathilde Bouchet, Arnauld Villers |
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| Přispěvatelé: | Mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Universitat Pompeu Fabra [Barcelona] (UPF), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle de Biologie Pathologie Génétique [CHU Lille], This work was in part supported by the Centre national de la recherche scientifique (CNRS), Ligue nationale contre le Cancer (Comité du Pas-de-Calais), Institut national du cancer (INCa_4419), Institut Pasteur de Lille, Conseil Régional du Nord-Pas-de-Calais and Fondation pour la Recherche Médicale (FRM), Conseil Régional du Nord-Pas-de-Calais, Association pour la Recherche sur le Cancer (ARC), MINECO (Juan de la Cierva Postdoctoral Fellowship FJCI-2014-22946), ARTP (Association de Recherche sur les tumeurs de prostate)., Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161 (M3T), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Service d'urologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), We would like to thank M. Tardivel, A. Bongiovanni and E. Werkmeister from the BioImaging Center Lille Nord de France (BICeL) for their technical assistance, M. Canouil for his statistics advice, and M. Vernier for his bioinformatic advice and stimulating discussions. We would also like to thank the local Tumor Tissue Bank (Tumorothèque), Regional Reference Oncology Center (CRRC) (Head, Pr. M.C. Copin) in Lille, France. |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Oncogene Proteins Fusion [SDV]Life Sciences [q-bio] MESH: Gene Expression Regulation Neoplastic Mice SCID urologic and male genital diseases Fusion gene MESH: Oncogene Proteins Fusion/metabolism Metastasis Prostate cancer 0302 clinical medicine MESH: Animals MESH: Mice SCID MESH: Osteoblasts/pathology ComputingMilieux_MISCELLANEOUS MESH: Prostatic Neoplasms/genetics Endothelin-1 Bone metastasis MESH: Prostatic Neoplasms/pathology Tumor Burden 3. Good health Gene Expression Regulation Neoplastic Phenotype Osteoblastic lesions Oncology 030220 oncology & carcinogenesis PC-3 Cells MESH: Bone Neoplasms/metabolism MESH: Bone Neoplasms/secondary MESH: PC-3 Cells MESH: Endothelin-1/metabolism Erg MESH: Alkaline Phosphatase/metabolism MESH: Cell Line Tumor Transplantation Heterologous MESH: Biomarkers Tumor/genetics MESH: Tumor Burden/genetics Bone Neoplasms [SDV.CAN]Life Sciences [q-bio]/Cancer Biology MESH: Phenotype TMPRSS2 MESH: Oncogene Proteins Fusion/genetics 03 medical and health sciences Transcriptional regulation Cell Line Tumor Biomarkers Tumor medicine Animals Humans MESH: Transplantation Heterologous MESH: Biomarkers Tumor/metabolism Osteoblasts MESH: Alkaline Phosphatase/genetics MESH: Humans MESH: Prostatic Neoplasms/metabolism Prostatic Neoplasms Gene rearrangement Alkaline Phosphatase MESH: Bone Neoplasms/genetics MESH: Osteoblasts/metabolism medicine.disease MESH: Male Collagen Type I alpha 1 Chain TMPRSS2:ERG 030104 developmental biology MESH: Endothelin-1/genetics Cancer research Ectopic expression |
| Zdroj: | Cancer Letters Cancer Letters, Elsevier, 2018, 438, pp.32-43. ⟨10.1016/j.canlet.2018.08.027⟩ Cancer Letters, 2018, 438, pp.32-43. ⟨10.1016/j.canlet.2018.08.027⟩ |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2018.08.027 |
| Popis: | International audience; Abstract : Prostate cancers have a strong propensity to metastasize to bone and promote osteoblastic lesions. TMPRSS2:ERG is the most frequent gene rearrangement identified in prostate cancer, but whether it is involved in prostate cancer bone metastases is largely unknown. We exploited an intratibial metastasis model to address this issue and we found that ectopic expression of the TMPRSS2:ERG fusion enhances the ability of prostate cancer cell lines to induce osteoblastic lesions by stimulating bone formation and inhibiting the osteolytic response. In line with these in vivo results, we demonstrate that the TMPRSS2:ERG fusion protein increases the expression of osteoblastic markers, including Collagen Type I Alpha 1 Chain and Alkaline Phosphatase, as well as Endothelin-1, a protein with a documented role in osteoblastic bone lesion formation. Moreover, we determined that the TMPRSS2:ERG fusion protein is bound to the regulatory regions of these genes in prostate cancer cell lines, and we report that the expression levels of these osteoblastic markers are correlated with the expression of the TMPRSS2:ERG fusion in patient metastasis samples. Taken together, our results reveal that the TMPRSS2:ERG gene fusion is involved in osteoblastic lesion formation induced by prostate cancer cells. |
| Databáze: | OpenAIRE |
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