Regulation of matrix metalloproteinase 13 expression by androgen in prostate cancer.
The matrix metalloproteinases (MMPs) are members of a family of endopeptidases that are able to degrade extra-cellular matrix. MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), play a key role in the migration of normal and malignant cell. Interaction of MMPs and TIMPs has been involved in the process of tumor invasion and metastasis. Using cDNA microarray as a screening tool to find androgen regulated gene in prostate cancer, we have found that expression of MMP-13 is regulated by androgen in prostate cancer derived cell line LNCaP. This regulation was further confirmed and quantified by real-time RT-PCR. In addition, the upregulation of MMP-13 mRNA by androgen could be abolished by the androgen antagonist Casodex but not the protein inhibitor cycloheximide. Western blot and immunohistochemistry of MMP-13 confirmed the androgen regulation at the protein level. We have furthermore shown that MMP-13 expression is presented in human prostate cancer obtained from aspiration biopsy. In summary, MMP-13 is androgen regulated and detectable in prostate cancer. Further study of MMP-13 in prostate cancer may help us to understand the progression of the cancer and can lead to new therapeutic options.
Pang
See-Tong
ST
Department of Molecular Medicine, Andrology centre, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Flores-Morales
Amilcar
A
Skoog
Lambert
L
Chuan
Yin-Choy
YC
Nordstedt
Gunnar
G
Pousette
Ake
A
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053509:Matrix Metalloproteinase 13; D009570:Nitriles; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014105:Tosyl Compounds; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014105:Tosyl Compounds; D003513:Cycloheximide; C053541:bicalutamide; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13