Stat3 enhances the growth of LNCaP human prostate cancer cells in intact and castrated male nude mice.
BACKGROUND
Prostate cancer frequently progresses from an initial androgen dependence to androgen independence, rendering the only effective androgen ablation therapy useless. The mechanism underlying the androgen-independent progression is unknown. Stat3, a member of the family of signal transducers and activators of transcription, is activated in numerous cancers, including prostate. This study is to investigate the role of Stat3 activation in the growth of prostate cancer cells.


METHODS
A constitutively active Stat3 was ectopically expressed in androgen-sensitive LNCaP prostate cancer cells and resulting stable clones expressing activated Stat3 were isolated. The effect of Stat3 activation on LNCaP cell growth in response to androgen in vitro and in vivo was examined.


RESULTS
We show that the levels of activated Stat3 are associated with the progression of androgen-independent prostate cancer. Activation of Stat3 in androgen-sensitive LNCaP prostate cancer cells results in enhancement of tumor growth in both intact and castrated male nude mice and enhances androgen receptor-mediated prostate specific antigen expression.


CONCLUSIONS
These findings demonstrate that intracellular signaling mediated by Stat3 can enhance the growth of androgen-sensitive human LNCaP prostate cancer cells in both intact and castrated male nude mice.
DeMiguel
Fernando
F
Department of Urology and Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Lee
Soo Ok
SO
Lou
Wei
W
Xiao
Xiao
X
Pflug
Beth R
BR
Nelson
Joel B
JB
Gao
Allen C
AC
D000728:Androgens / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators