Low androgen sensitivity is associated with low levels of Akt phosphorylation in LNCaP-E9 cells.

We previously characterized LNCaP-E9, a low-androgen-sensitive LNCaP cell subline. LNCaP-E9 cells exhibit lower expression of androgen-regulated genes, including prostate-specific antigen (PSA), FK506 binding protein 5 (FKBP5), and prostatic acid phosphatase (PAcP), compared with LNCaP cells after treatment with the synthetic androgen R1881, confirming that the cells have low sensitivity to androgens. To understand the mechanism underlying low androgen sensitivity of LNCaP-E9 cells, we examined the activities of the Akt, p44/42, and p38 mitogen-activated protein kinase signaling pathways, all of which are known to be linked to androgen receptor signaling. We found that the phosphorylation of Akt at Ser473 was markedly lower in LNCaP-E9 cells than in LNCaP cells. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase inhibitor LY294002 resulted in reduction of PSA expression in LNCaP cells. Conversely, activation of Akt by serum starvation led to the induction of PSA expression in LNCaP-E9 cells. These results suggest that the impaired Akt phosphorylation in LNCaP-E9 cells is associated with low androgen sensitivity.