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.
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Kazuhiro
K
Iguchi
Kazuhiro
K
Fukami
Kenichiro
K
Ishii
Takashi
T
Otsuka
Shigeyuki
S
Usui
Yoshiki
Y
Sugimura
Kazuyuki
K
Hirano
D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D000728:Androgens; D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt