Regulation of prostate-specific antigen expression by the junctional adhesion molecule A.
OBJECTIVE
Prostate-specific antigen (PSA) is a protein specifically expressed in prostate cells. Therefore, the expression levels of PSA in the blood are an important indicator when diagnosing prostate cancer. Defining the mechanism of PSA expression in prostate cells will be helpful for interpreting the expression of this protein during prostate cancer progression. Reports show that a membrane protein, claudin-7 (CLDN-7), is involved in the expression of PSA. However, the mechanism by which CLDN-7 regulates PSA expression is not clear. Here we identify proteins that interact with CLDN-7 and determine whether such proteins can regulate PSA expression in a pattern similar to that of CLDN-7.


METHODS
Our previous studies have demonstrated that in prostate cells, PSA can be regulated by a membrane protein, CLDN-7. It is important to identify the proteins that associate with CLDN-7 in its pathway of regulating PSA expression, because it is very unlikely that CLDN-7 can directly regulate PSA expression in the nucleus. To identify potential proteins that may directly interact with CLDN-7, we studied proteins that can interact with claudins.


RESULTS
We found that CLDN-7 interacts with the junctional adhesion molecule A (JAM-A), which is expressed in the prostate cancer cell line, LNCaP, which expresses PSA, but not the PSA-negative prostate cell line, DU145. JAM-A regulates the expression of the prostate-specific antigen in LNCaP cells in a pattern similar to CLDN-7.


CONCLUSIONS
Our results suggest that JAM-A associates with CLDN-7 and it is a component in the pathway by which CLDN-7 regulates the expression of PSA.
Wang
Qiuwei
Q
University of California-Los Angeles Dental Research Institute and University of California-Los Angeles School of Dentistry, Los Angeles, California 90095-1668 , USA.
Zheng
Jun-Ying
JY
Kreth
Jens
J
Yan
Xinmin
X
Kamata
Masakazu
M
Campbell
Richard A
RA
Xie
Yiming
Y
Chiu
Robert
R
Berenson
James R
JR
Shi
Wenyuan
W
Chen
Irvin S Y
IS
Pang
Shen
S
D014408:Biomarkers, Tumor / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000378:metabolism; D057167:Claudins; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D062726:Junctional Adhesion Molecules; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D014162:Transfection; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C473255:CLDN7 protein, human; D015815:Cell Adhesion Molecules; D057167:Claudins; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen