Genistein-induced neuroendocrine differentiation of prostate cancer cells.
BACKGROUND
Neuroendocrine (NE) cells are present in normal prostate and their number appears to be increased in advanced prostate cancer (PCA). In this study, we studied the effect of the phytoestrogen, genistein, on NE differentiation of LNCaP cells in vitro.


METHODS
Neuroendocrine marker expression of LNCaP cells exposed to genistein was measured by immunohistochemistry, Western blot, and real-time PCR methods. Western blot analysis was used to study cell cycle and signaling pathways induced by genistein treatment.


RESULTS
Six days after continuous genistein treatment, the majority of genistein-surviving cancer cells underwent transdifferentiation into a NE-like phenotype overexpressing the NE markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE differentiation process was associated with upregulation of the cell cycle modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways.


CONCLUSIONS
Our data indicate that genistein evokes not only apoptosis but also NE transdifferentiation of PCA cells.
Pinski
Jacek
J
Division of Medical Oncology, University of Southern California Keck School of Medicine, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. pinski_j@ccnt.hsc.usc.edu
Wang
Qingcai
Q
Quek
Marcus L
ML
Cole
Ariana
A
Cooc
Janine
J
Danenberg
Kathleen
K
Danenberg
Peter V
PV
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology; D017077:Culture Media, Conditioned; D000077143:Docetaxel; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009490:Neurosecretory Systems / Q000473:pathology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D043823:Taxoids / Q000494:pharmacology
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D043823:Taxoids; D000077143:Docetaxel; D019833:Genistein; D020928:Mitogen-Activated Protein Kinases