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- W2900599233 abstract "2962 BACKGROUND. Elevated levels of versican are observed in the stroma surrounding prostate cancer, and have been identified as an indicator of progression in the early stage of this disease. It has been suggested that increased versican expression in prostatic stromal cells is induced by tumour-derived TGFβ1. A sub-group of the ADAMTS lineage of metalloproteases that possess versican-degrading properties are also potential regulators of proteoglycan accumulation in prostate cancer. These enzymes have one major inhibitor in the extracellular matrix; tissue inhibitor of metalloproteinases (TIMP)-3. In this study, we have assessed the in vitro effect of TGFβ1 on the expression of ADAMTS proteoglycanases, versican and TIMP-3 in prostatic stromal cells. METHODS. Four prostatic stromal cell lines were isolated, characterised and maintained as short-term cultures (up to 10 passages) from benign prostatic hyperplasia patients undergoing TURP for urinary obstruction. The effect of TGFβ1 on mRNA expression in prostatic stromal cells was determined by Real-Time RT-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. All prostatic stromal cell cultures consistently expressed ADAMTS-1, -4, -5, -9, -15 and TIMP-3, in contrast to PC3, DU145 and LNCaP prostate cancer cells cells which failed to express 2 or more ADAMTS transcripts. ADAMTS-1 and -5 were most abundant in stromal cells, whereas ADAMTS-4 was expressed only at very low levels compared to other ADAMTS transcripts. In stromal cells, TGFβ1 significantly decreased ADAMTS-1, -5, -9 and -15 expression and increased versican and TIMP-3 (p in vivo . The latter may therefore be a surrogate effect of TGFβ1 over-expression in this disease." @default.
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- W2900599233 date "2005-05-01" @default.
- W2900599233 modified "2023-09-26" @default.
- W2900599233 title "The expression and regulation of ADAMTS proteoglycanases and TIMP-3 by TGFβ1: Relevance to the accumulation of versican in prostate cancer" @default.
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