[Molecular mechanisms involved in hormone resistance of prostate cancer].
Prostate cancer has an androgen-dependent growth mediated by the androgen receptor (AR). Androgen pathway blockage is the standard therapy for the treatment of prostate cancers at an advanced stage. In spite of an initial sensitivity, prostate cancers become more or less quickly towards androgen-independent. Hormone refractory can be due to amplification of AR gene, AR mutations and the increase in co-activator protein expression or in the 5alpha-reductase activity. These induce an agonist activity with the anti-androgens or others steroid hormones like estrogens on AR and allow AR activation with weak concentrations of androgens. Growth factors and cytokines can induce AR phosphorylation independently of the ligand fixation. In condition of androgenic deprivation, AR remains actively involved in the growth of the cancerous cells prostate. Nevertheless, there are others partial AR-independent pathways as neuroendocrine differentiation. The comprehension of these various mechanisms is the key of the development of more effective therapies on hormono-refractory prostate cancers.
Cabrespine
Aurélie
A
Centre Jean-Perrin, Clermont-Ferrand. recherche.clinique@cjp.fr
Guy
Laurent
L
Chollet
Philippe
P
Debiton
Eric
E
Bay
Jacques-Olivier
JO
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000502:physiology; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009490:Neurosecretory Systems / Q000473:pathology; D009919:Orchiectomy; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D066247:Receptor, ErbB-4; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D014183:Transplantation, Heterologous
D000726:Androgen Antagonists; D000728:Androgens; D006133:Growth Substances; D007378:Interleukins; D011944:Receptors, Androgen; D017978:Receptors, Growth Factor; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4