AMP-activated protein kinase promotes human prostate cancer cell growth and survival.
The molecular mechanisms underlying the development and progression of prostate cancer are poorly understood. AMP-activated protein kinase (AMPK) is a serine-threonine kinase that is activated in response to the hypoxic conditions found in human prostate cancers. In response to energy depletion, AMPK activation promotes metabolic changes to maintain cell proliferation and survival. Here, we report prevalent activation of AMPK in human prostate cancers and provide evidence that inhibition or depletion of AMPK leads to decreased cell proliferation and increased cell death. AMPK was highly activated in 40% of human prostate cancer specimens examined. Endogenous AMPK was active in both the androgen-sensitive LNCaP cells and the androgen-independent CWR22Rv1 human prostate cancer cells. Depletion of AMPK catalytic subunits by small interfering RNA or inhibition of AMPK activity with a small-molecule AMPK inhibitor (compound C) suppresses human prostate cancer cell proliferation. Apoptotic cell death was induced in LNCaP and CWR22Rv1 cells at compound C concentrations that inhibited AMPK activity. The evidence provided here is the first report that the activated AMPK pathway is involved in the growth and survival of human prostate cancer and offers novel potential targets for chemoprevention of human prostate cancer.
Department of Radiation Medicine, Georgetown University Medical Center, Georgetown University Hospital, Lower Level, Bles Building, 3800 Reservoir Road Northwest, Washington, DC 20007, USA.
Hyeon Ung
HU
Park
Simeng
S
Suy
Malika
M
Danner
Vernon
V
Dailey
Ying
Y
Zhang
Henghong
H
Li
Daniel R
DR
Hyduke
Brian T
BT
Collins
Gregory
G
Gagnon
Bhaskar
B
Kallakury
Deepak
D
Kumar
Milton L
ML
Brown
Albert
A
Fornace
Anatoly
A
Dritschilo
Sean P
SP
Collins
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins; D006801:Humans; D008297:Male; D051379:Mice; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C493245:CRTC2 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D055372:AMP-Activated Protein Kinases