Estrogen-dependent regulation of prolidase activity in breast cancer MCF-7cells

Prolidase [EC 3.4. 13.9] plays an important role in the recycling of prolin e for collagen synthesis and cell growth. The increase in the enzyme activi ty is correlated with the increased intensity of collagen turnover, thus re flecting the intensity of collagen metabolism. Since estrogens alter collag en metabolism, it can be assumed that the changes may be reflected by proli dase activity. The effects of estrogen and antiestrogen (tamoxifen on the p rolidase and collagenase activities and collagen biosynthesis) were measure d in the estrogen-receptor (ER)-positive breast cancer cell line. Estradiol stimulated collagen biosynthesis and extracellular prolidase and collagena se activities in cultured MCF-7 cells without an effect on collagen accumul ation in the extracellular matrix produced by these cells. On the other han d, tamoxifen inhibited the estrogen-dependent stimulatory effect on collage n biosynthesis but did not inhibit the stimulatory effect of estrogen on pr olidase and collagenase activities. The inhibitory effect of tamoxifen on e strogen-dependent stimulation of collagen synthesis in MCF-7 cells and lack of its effect on estrogen-dependent stimulation of prolidase and collagena se activities suggest that both processes (collagen synthesis and degradati on) are independently regulated in MCF-7 cells, possibly through antagonist , agonist and other estrogen receptor-independent actions of tamoxifen. Inc reased extracellular prolidase activity in estrogen-stimulated MCF-7 cells indicates potential diagnostic value of tissue prolidase in determining the ER status of breast cancer.