Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells.
OBJECTIVE
Neuroendocrine (NE) cells were thought to be post-mitotic and non-proliferative. But it was recently reported that NE cells express, and induce surrounding cells to express potent antiapoptotic proteins. We hypothesize that neuroendocrine differentiation (NED), a common phenomenon in prostate cancer, is related to chemoresistance in prostate cancer.


METHODS
Androgen-independent human prostate cancer DU145 and PC-3 cells were exposed to epidermal growth factor (EGF). MTT assays evaluated changes in chemoresistance after EGF treatment, and flow cytometry examined EGF-induced cell cycle changes in DU145 cells. Western blotting, real-time RT-PCR and transmission electron microscopy were utilized to confirm NED.


RESULTS
After stimulation with EGF, DU145 and PC-3 cells exhibited stronger resistance to cisplatin. Flow cytometry showed that EGF stimulation substantially decreased the proportion of DU145 cells in G(1) phase. EGF treatment increased the expression of neuron-specific enolase, a marker of NED induction.


CONCLUSIONS
NED in prostate cancer is involved in the chemoresistance induced by EGF. EGF and/or the EGF receptor may be potential targets for medical intervention in chemo-resistant prostate cancer.
Li
Yuan
Y
Department of Urology, Xiang Ya Hospital, Central South University, PR China.
Chen
He Qun
HQ
Chen
Min Feng
MF
Liu
Huai Zheng
HZ
Dai
Yuan Qing
YQ
Lv
Hui
H
Bing Zu
Xiong
X
Qi
Lin
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D055099:Neuroendocrine Cells / Q000166:cytology* / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D010751:Phosphopyruvate Hydratase; D002945:Cisplatin