The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?
The nuclear factor of kappa beta (NF-kappaB) transcription factor regulates the transcription of numerous genes including that of interleukin 6 (IL-6). The IL-6 acts as an autocrine and paracrine growth factor of androgen-independent prostate cancer. An aberrant expression of the IL-6 gene and an increase in IL-6 expression are detected in bone metastatic and hormone-refractory prostate cancer. IL-6 has been suggested to have a crucial role in the resistance to chemotherapy or hormonal therapy involving apoptotic cell death. The NF-kappaB/IL-6 dependent pathways promote tumour-cell survival and in most situations protect cells against apoptotic stimuli. These data provide a rational framework for targeting NF-kappaB and IL-6 activity in novel biologically based therapies for aggressive and androgen independent prostate cancers.
Paule
Bernard
B
AP-HP, Groupe Hospitalier Henri Mondor, Service d'Urologie, 94000 Créteil, France.
Terry
Stéphane
S
Kheuang
Laurence
L
Soyeux
Pascale
P
Vacherot
Francis
F
de la Taille
Alexandre
A
D001859:Bone Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
D015850:Interleukin-6; D016328:NF-kappa B