التفاصيل البيبلوغرافية
| العنوان: |
Characterization of Pten and Trp53 deficient prostatic tumors in mice ; Caractérisation des tumeurs prostatiques déficientes pour Pten et Trp53 chez la souris |
| المؤلفون: |
El Bizri, Rana |
| المساهمون: |
Strasbourg, Metzger, Daniel, Daher, Ahmad |
| المصدر: |
Theses.fr |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
Cancer de la prostate, Cellules épithéliales prostatiques, Néoplasmes prostatiques intraépithéliaux, Sénescence cellulaire, Stress réplicatif, Une réponse aux dommages de l’ADN, Cancers de la prostate résistants à la castration, Prostate cancer, Prostatic epithelial cells, Prostatic intraepithelial neoplasia, Cell senescence, Replication stress, DNA damage response, Castration-resistant prostate cancer, envir, psy |
| الوصف: |
Prostate cancer (PCa) is a leading cause of male cancer death worldwide. While most locally PCa are curable, metastatic tumors initially respond to androgen deprivation therapy but ultimately relapse to castration-resistant prostate cancer (CRPC), which is a lethal disease. Since the tumor suppressor genes PTEN and p53 are frequently mutated in metastatic and CRPC, the host laboratory generated mouse models in which Pten and/or Trp53 are selectively ablated in adult prostatic epithelial cells (PECs) in order to unravel the key events leading to prostate cancer progression. Our study reveals that Pten ablation stimulates PECs proliferation forming prostatic intraepithelial neoplasia (PIN) within a few months. This hyper-proliferation induces replicative stress and a DNA damage response (DDR), which in turn leads to a progressive growth arrest with characteristics of cell senescence. As senescent cells secrete a large number of cytokines and chemokines, and can accumulate other mutations, they might contribute to tumor progression. Importantly, in the absence of Trp53, most Pten-null PECs develop PINs that enter senescence. However partial loss of PECs identity is detected as we show enhanced stemness and focal neuroendocrine differentiation of luminal Pten-null PECs. In some cases, adenocarcinoma and sarcomatoid tumors are formed, and more than one-third of the latter develop metastases. Strikingly, we also show formation of a castrate-resistant cell entity of both Pten and Pten/Trp53-null PECs sharing luminal and basal markers. Taken together, as current treaments lead to side effects and resistance, the development of therapeutic strategies to eliminate senescent cells/and or PECs expressing luminal and basal/stem progenitor in pre- cancerous lesions represents promising option for prostate cancer treatment. ; Le cancer de la prostate est la forme de cancer la plus fréquente et la troisième cause de décès par cancer chez l’homme dans les sociétés occidentales. Alors que la plupart des cancers de la prostate ... |
| نوع الوثيقة: |
thesis |
| اللغة: |
English |
| العلاقة: |
10670/1.jofsyk; http://www.theses.fr/2018STRAJ097/documentTest |
| الإتاحة: |
http://www.theses.fr/2018STRAJ097/documentTest |
| حقوق: |
other |
| رقم الانضمام: |
edsbas.C1F36835 |
| قاعدة البيانات: |
BASE |
