Autophagy protects LNCaP cells under androgen deprivation conditions.
Androgen plays a critical role in the development and progression of prostate cancer. However, the regulatory role of androgen in the autophagic process and the function of the increased autophagosomes following androgen deprivation remain poorly understood. We found that autophagosomes, which were induced upon serum deprivation in LNCaP cells, can be significantly suppressed by dihydrotestosterone (DHT). Pharmacological inhibition of autophagy by 3-methyladenine led to increased apoptosis of LNCaP cells in serum-free medium compared to the medium with DHT or serum. Additionally, depletion of Beclin 1 to inhibit autophagy by small interfering RNA resulted in a slower proliferation of LNCaP cells in the medium depleted of serum than in the medium with DHT. Altogether, these findings suggested that LNCaP cells can resort to the autophagic pathway to survive under androgen deprivation conditions, which can be a novel mechanism involved in the transition of prostate cancer cells from an androgen-dependent to an androgen-independent cell type.
Li
Mengqiang
M
The Department of Urology, Peking University First Hospital, Peking University, The Institute of Urology, Peking University, Beijing, China.
Jiang
Xuejun
X
Liu
Di
D
Na
Yanqun
Y
Gao
George F
GF
Xi
Zhijun
Z
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D048430:Cell Shape; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011471:Prostatic Neoplasms; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D016895:Culture Media, Serum-Free; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D013196:Dihydrotestosterone