RESUMEN
PURPOSE: To determine whether the up-regulation of the differentiation related gene (Drg-1) enhances the progression of prostate cancer into the androgen independent phenotype, via escaping androgen signal transduction. MATERIALS AND METHODS: A full length of Drg-1 cDNA was obtained using the Drg-1 primer, which was inserted into LNCaP cells. The sensitivities of dihydrotestosterone and bicalutamide were then examined. In addition, the level of the Drg-1 gene expression was examined in derivatives of the LNCaP cell lines obtained from the orthotopic animal model. RESULTS: The Drg-1 transfected LNCaP cells, which highly expressed the Drg-1, were established (LNCaP/D2). The LNCaP/D2 slowly grew in a culture medium, supplemented with 10% charcoal stripped fetal bovine serum, whereas the control cells did not. When the sensitivities of DHT and bicalutamide were examined, the PC-3 and LNCaP/D2 cells were not sensitive to either. The metastatic androgen independent prostate cancer cells (LNCaP-AI-Lung), which were obtained from the orthotopic animal model, showed higher levels of Drg-1 expression than the parental cells. CONCLUSIONS: Androgen dependent prostate cancer cells, expressing high levels of the Drg-1 gene, behave like androgen independent prostate cancer cells. This finding suggest that the Drg-1 gene may play an important role in the initiation of an androgen-independent state.