Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera.
The ability to identify prostate tumor or prostate tissue specific genes that are expressed at high levels and use their protein products as targets could greatly aid in the diagnosis and treatment of prostate cancer. Using a polymerase chain reaction (PCR)-based subtraction technique, we have recovered the recently described KLK4 (prostase) gene from human prostate cDNA. In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples. Quantitative mRNA analysis also demonstrated low level expression including adrenal gland, salivary gland and thyroid. Finally, it was demonstrated that prostate cancer patient sera contain antibodies that bind specifically to recombinant KLK4 protein. This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments. The relatively specific expression profile and elevated level of KLK4 mRNA and protein in both tumor and normal prostate tissues, in addition to detectable KLK4-specific antibody in cancer patient sera, supports additional efforts to determine if KLK4 can play a role in the diagnosis of prostate cancer, the monitoring of residual disease, or act as a target for immunotherapy.
Day
Craig H
CH
Corixa Corporation, 1124 Columbia Street, Suite 200, Seattle, Washington, WA 98104, USA. day@corixa.com
Fanger
Gary R
GR
Retter
Marc W
MW
Hylander
Bonnie L
BL
Penetrante
Remedios B
RB
Houghton
Raymond L
RL
Zhang
Xinqun
X
McNeill
Patricia D
PD
Filho
Aristides Maltez
AM
Nolasco
Marcos
M
Badaro
Roberto
R
Cheever
Martin A
MA
Reed
Steven G
SG
Dillon
Davin C
DC
Watanabe
Yoshihiro
Y
D000906:Antibodies / Q000097:blood*; D001943:Breast Neoplasms / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D008297:Male; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis
D000906:Antibodies; D012333:RNA, Messenger; D007610:Kallikreins; C120801:kallikrein 4