mRNA expression profile of matrix metalloproteinases and their tissue inhibitors in malignant and non-malignant prostatic tissue.
BACKGROUND
Increased expression of matrix metalloproteinases (MMPs) was found in various carcinomas. The aim of this study was to present a comprehensive mRNA expression profile of MMPs in benign and malignant prostatic tissue.


METHODS
mRNA expression patterns of MMP-1, -2, -7, -9, -11, -14 and their tissue inhibitors (TIMPs) -1, -2 and -3 were studied in cancerous and non-cancerous parts of 17 prostates removed by radical prostatectomy. Competitive reverse transcritpion PCR was used for quantification of MMP and TIMP mRNA.


RESULTS
Both decreased (MMP-2, MMP-11, MMP-14) and a tendency to increased (MMP-9) MMP values in cancerous compared to the non-cancerous samples were observed. Significantly reduced TIMP-2 and TIMP-3 values were remarkable. Relatively strong associations were found among the three TIMPs while only a significant correlation between MMPs was observed between MMP-2 and MMP-7. There were no significant correlations between MMPs and tumor grade and stage and serum prostate-specific antigen. Receiver operation characteristic analyses proved that MMP and TIMP mRNA and their ratios have an insufficient capability to differentiate between cancerous and non-cancerous tissue. The ratios of MMP-9 to all three TIMPs and the ratio of MMP-14 to TIMP-3 were significantly increased.


CONCLUSIONS
These increased ratios support the view of an imbalance between MMP-9 activity and its inhibitory counterparts in cancerous tissue as an important step in the development of prostate carcinoma and implicate the rationale of using synthetic inhibitors of MMPs as potential therapeutic tools.
Lichtinghagen
Ralf
R
Department of Clinical Chemistry, University Medical School, Hannover, Germany.
Musholt
Petra B
PB
Stephan
Carsten
C
Lein
Michael
M
Kristiansen
Glen
G
Hauptmann
Steffen
S
Rudolph
Birgit
B
Schnorr
Dietmar
D
Loening
Stefan A
SA
Jung
Klaus
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000368:Aged; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases