Activation of extracellular signal-regulated kinase in human prostate cancer.
OBJECTIVE
To investigate the level of expression, activation state, and functional significance of extracellular signal regulated kinase (ERK) in prostate cancer.


METHODS
Human prostate tissue samples (n = 22) were obtained from patients undergoing radical prostatectomy for localized adenocarcinoma of the prostate (n = 16, age range 44 to 72 years) or normal prostate specimens (n = 6, age ranges 19 to 47 years) obtained from rapid autopsy. Immunoblots, in vitro kinase assays, and immunohistochemistry were used to determine the expression and activation state of ERK in human prostate cancer.


RESULTS
Immunoblot and in vitro kinase assays demonstrated a 15-fold increase in ERK activation in prostate cancer specimens compared with normal human prostate tissue; however, ERK expression levels were only 1.3-fold higher in cancer. Immunohistochemical analysis demonstrated similar expression of ERK in cancer and normal tissues; however, phosphorylated ERK demonstrated greater intensity in the cancer specimens. Experiments conducted on a prostate cancer cell line demonstrated that EGF induced activation of ERK and cellular proliferation was partially inhibited by PD98059, a chemical inhibitor of the immediate upstream signaling component responsible of activation of ERK.


CONCLUSIONS
Collectively, these data demonstrate a dramatic increase in ERK activation in prostate cancer compared with normal prostate tissue and suggest that inhibitors designed to target this signal transduction cascade might have therapeutic benefit in the treatment of prostate cancer.
Price
D T
DT
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Della Rocca
G
G
Guo
C
C
Ballo
M S
MS
Schwinn
D A
DA
Luttrell
L M
LM
D000230:Adenocarcinoma / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism*; D002455:Cell Division; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases