Role of MMP in prostate cancer

Growth factors and receptor kinases can also influence transcriptional regulation of MMPs. MMPs have been shown to play a significant role in prostate cancer metastasis (Wood et al., 1997; Sehgal et al, 1998; Pajouh et al, 1991; Powell et al, 1993). Moreover, recent evidence suggests an increase in MMP-2 and TIMP-2 ratio is associated with high-grade and high-stage prostate tumors (Still et al., 2000). MMP expression could be induced by two possible mechanisms. First, prostate stromal cells could secrete growth factors such as epidermal growth factor (EGF) and induce expression of downstream effectors such as metalloprotei-nases. Growth factors and their receptors have been shown to be key components of tumor development and progression (Sundareshan et al., 1999). Epidermal growth factor receptor (EGFR) expression in bladder cancer cells, for example, is associated with high tumor stage and grade (Nutt et al., 1998). EGF has been shown to induce the AP-1 transcriptional regulatory complex, which transcriptionally activates MMP-1 expression and MMP-3 expression in fibroblasts. EGFR stimulation promotes both breast cancer cell migration (Price et al., 1999) and induces MMP-1 expresssion (Nutt and Lunec, 1996). Second, MMP expression is also regulated by E-cadherin expression (Nawrocki-Raby et al., 2003). Restoration of E-cad-herin expression in E-cadherin negative Dunning rat prostate tumor cells inhibits in vitro invasion and MMP-2 activity in these cells (Luo et al., 1999).

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