Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells

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. 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. 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 G1 phase. EGF treatment increased the expression of neuron-specific enolase, a marker of NED induction. 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.