Web of Science: 13 citas, Scopus: 15 citas, Google Scholar: citas
Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells
Cánovas, Verónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Puñal, Yolanda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Maggio, Valentina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Redondo, Enric (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Marín, Mercedes (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Mellado, Begoña (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Olivan, M. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lleonart, Matilde (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Planas, Jacques (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Morote Robles, Juan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Paciucci, Rosanna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha: 2017
Resumen: Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B). In addition, PTOV1 induced prostatospheres formation and self-renewal genes expression (ALDH1A1, LIN28A, MYC and NANOG). In contrast, Du145 and PC3 cells knockdown for PTOV1 significantly accumulated in the G2/M phase, presented a concomitant increased subG1 peak, and cell death by apoptosis. These effects were enhanced in docetaxel-resistant cells. Analyses of tumor datasets show that PTOV1 expression significantly correlated with prostate tumor grade, drug resistance (CCNG2) and self-renewal (ALDH1A1, MYC) markers. These genes are concurrently overexpressed in most metastatic lesions. Metastases also show PTOV1 genomic amplification in significant co-occurrence with docetaxel-resistance and self-renewal genes. Our findings identify PTOV1 as a promoter of docetaxel-resistance and self-renewal characteristics for castration resistant prostate cancer. The concomitant increased expression of PTOV1, ALDH1A1 and CCNG2 in primary tumors, may predict metastasis and bad prognosis.
Ayudas: Ministerio de Economía y Competitividad SAF2014-59958-R
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR733
Instituto de Salud Carlos III RD12-0036-0035
Instituto de Salud Carlos III PI15-00676
Instituto de Salud Carlos III PI12-01226
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Materia: PTOV1 ; Docetaxel resistance ; Prostate cancer ; Metastasis ; Apoptosis
Publicado en: Oncotarget, Vol. 8 (july 2017) , p. 59165-59180, ISSN 1949-2553

DOI: 10.18632/oncotarget.19467
PMID: 28938627


16 p, 5.8 MB

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