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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican.

BACKGROUND: Benign prostatic hyperplasia (BPH) is characterized by a proportional increase in the size of the stromal compartment of the gland, involving alterations to extracellular matrix ( ECM) components. Some of these changes have been associated with the activity and expression of transforming growth factor beta1 (TGFbeta1). Versican (chondroitin sulphate proteoglycan-2) is overexpressed in BPH and prostate cancer and potentially contributes to disease pathology. A sub-group of the ADAMTS lineage of metalloproteases possess versican-degrading properties and are potential regulators of proteoglycan accumulation associated with BPH. These enzymes have one major inhibitor in the ECM, tissue inhibitor of metalloproteinases (TIMP)-3. METHODS: The effect of TGFbeta on mRNA expression in prostatic stromal cells was determined by real-time qRT-PCR using primers to ADAMTS-1, -4, -5, -9, -15, versican, and TIMP-3. MMP-inhibitory potential (TIMP activity) of conditioned medium was measured using a fluorometric peptide substrate. RESULTS: Prostatic stromal cell cultures consistently expressed ADAMTS-1, -4, -5, -9, -15 and TIMP-3, in contrast to PC3, DU145, and LNCaP cells which failed to express at least two ADAMTS transcripts. In stromal cells, TGFbeta1 decreased ADAMTS-1, -5, -9, and -15 transcripts and increased ADAMTS-4, versican, and TIMP-3. TGFbeta also increased TIMP activity in conditioned medium. CONCLUSIONS: The induction of versican expression by TGFbeta in BPH stromal cells is in agreement with histological studies. The negative effect of TGFbeta1 on ADAMTS-1, -5, -9, and -15 coupled with increases in their inhibitor, TIMP-3 may aid the accumulation of versican in the stromal compartment of the prostate in BPH and prostate cancer.[1]


  1. The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican. Cross, N.A., Chandrasekharan, S., Jokonya, N., Fowles, A., Hamdy, F.C., Buttle, D.J., Eaton, C.L. Prostate (2005) [Pubmed]
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