Prolonged exposure to ( R )-bicalutamide generates a LNCaP subclone with alteration of mitochondrial genome

Autor: Chiara Arienti, Valentina Casadio, Marzia Di Donato, Ugo De Giorgi, Gabriella Castoria, Mirella Falconi, Sara Pignatta, Wainer Zoli, Elisa Gabucci, Anna Tesei, Rosella Silvestrini
Přispěvatelé: Sara, Pignatta, Chiara, Arienti, Wainer, Zoli, DI DONATO, Marzia, Castoria, Gabriella, Elisa, Gabucci, Valentina, Casadio, Mirella, Falconi, Ugo De Giorgi, Rosella, Silvestrini, Anna, Tesei, Sara Pignatta, Chiara Arienti, Wainer Zoli, Marzia Di Donato, Gabriella Castoria, Elisa Gabucci, Valentina Casadio, Mirella Falconi, Rosella Silvestrini, Anna Tesei
Rok vydání: 2014
Předmět:
Male
Transcription
Genetic
ormono-indipendenza
Respiratory chain
Hormone-resistance
urologic and male genital diseases
Mitochondrial Dynamics
Biochemistry
GTP Phosphohydrolases
Tosyl Compounds
Androgen deprivation therapy
Prostate cancer
Endocrinology
MTDNA
Chlorocebus aethiops
Anilides
mitochondrial network
Mitochondrial fission
prostate cancer
Phenotype
hormone-independent progression
Gene Expression Regulation
Neoplastic
COS Cells
Androgens
Microtubule-Associated Proteins
tumori della prostata
medicine.drug
Dynamins
Mitochondrial DNA
(R)-bicalutamide
Bicalutamide
Cell Survival
network mitocondriale
Biology
DNA
Mitochondrial
Mitochondrial Proteins
Cell Line
Tumor
Nitriles
LNCaP
medicine
Animals
Humans
Molecular Biology
Gene Expression Profiling
Prostatic Neoplasms
medicine.disease
Molecular biology
Clone Cells
Drug Resistance
Neoplasm
Genome
Mitochondrial
Zdroj: Molecular and Cellular Endocrinology. 382:314-324
ISSN: 0303-7207
DOI: 10.1016/j.mce.2013.10.022
Popis: Advanced prostate cancers, initially sensitive to androgen deprivation therapy, frequently progress to the castration-resistant prostate cancer phenotype (CRPC) through mechanisms not yet fully understood. In this study we investigated mitochondrial involvement in the establishment of refractoriness to hormone therapy. Two human prostate cancer cell lines were used, the parental LNCaP and the resistant LNCaP-Rbic, the latter generated after continuous exposure to 20 μM of (R)-bicalutamide, the active enantiomer of Casodex®. We observed a significant decrease in mtDNA content and a lower expression of 8 mitochondria-encoded gene transcripts involved in respiratory chain complexes in both cell lines. We also found that (R)-bicalutamide differentially modulated dynamin-related protein (Drp-1) expression in LNCaP and LNCaP-Rbic cells. These data seem to indicate that the androgen-independent phenotype in our experimental model was due, at least in part, to alterations in mitochondrial dynamics and to a breakdown in the Drp-1-mediated mitochondrial network.
Databáze: OpenAIRE
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