Role of androgen receptor in the pathogenesis of human prostate cancer

AIM: To investigate molecular mechanisms associated with the acquisition of androgen-independent growth of human prostate cancer during progression. METHODS: Upon continuously passaging, the androgen-independent LNCaP cell model was established. The expression of AR and PSA proteins in the course of prostate cancer progression was determined by Western blot. RESULTS: Upon continuous passage, the biological behavior of androgen-dependent parental LNCaP C-33 cells (passage number less than 33) was altered. LNCaP C-81 cells (passage number higher than 80) exhibited more aggressive growth and lower androgen-dependence than C-33 and C-51 cells (passage number between 33 and 80). C-81 cells secreted a higher level of PSA and the degree of DHT stimulation on PSA secretion was lower in C-81 cells than C-33 cells. The three LNCaP subclones expressed a similar level of total AR protein, but C-81 cells showed a characteristic loss of expression of the AR-B and increase in expression of the AR-A. CONCLUSION: Multiple factors, including the different expression of AR isoforms, contribute to the development of androgen-independent growth of prostatic carcinoma cells.