Estrogen-dependent regulation of prolidase activity in breast cancer MCF-7 cells.
Prolidase [EC 3.4.13.9] plays an important role in the recycling of proline for collagen synthesis and cell growth. The increase in the enzyme activity is correlated with the increased intensity of collagen turnover, thus reflecting the intensity of collagen metabolism. Since estrogens alter collagen metabolism, it can be assumed that the changes may be reflected by prolidase activity. The effects of estrogen and antiestrogen (tamoxifen on the prolidase and collagenase activities and collagen biosynthesis) were measured in the estrogen-receptor (ER)-positive breast cancer cell line. Estradiol stimulated collagen biosynthesis and extracellular prolidase and collagenase activities in cultured MCF-7 cells without an effect on collagen accumulation in the extracellular matrix produced by these cells. On the other hand, tamoxifen inhibited the estrogen-dependent stimulatory effect on collagen biosynthesis but did not inhibit the stimulatory effect of estrogen on prolidase and collagenase activities. The inhibitory effect of tamoxifen on estrogen-dependent stimulation of collagen synthesis in MCF-7 cells and lack of its effect on estrogen-dependent stimulation of prolidase and collagenase activities suggest that both processes (collagen synthesis and degradation) are independently regulated in MCF-7 cells, possibly through antagonist, agonist and other estrogen receptor-independent actions of tamoxifen. Increased extracellular prolidase activity in estrogen-stimulated MCF-7 cells indicates potential diagnostic value of tissue prolidase in determining the ER status of breast cancer.
Miltyk
W
W
Department of Medicinal Chemistry, Medical University of Bialystok, Poland.
Anchim
T
T
Wolczynski
S
S
Palka
J
J
D001943:Breast Neoplasms / Q000201:enzymology*; D003094:Collagen / Q000096:biosynthesis; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D004150:Dipeptidases / Q000187:drug effects* / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase; D017364:Collagenases