Elastases in human breast carcinoma cell lines.
Elastosis, the deposition of large amounts of elastin, is characteristic of the desmoplastic reaction to human breast carcinoma. Dissolution of the elastin often occurs following treatment regimens that involve steroid hormones or their antagonists. Elastinolytic activities must be invoked to account for the loss of this elastin-cotaining stroma. We have utilized a tissue culture model to explore the molecular aspects of this phenomenon. The elastases of several human fibroblast and breast carcinoma cell lines were examined. The tumor cells had 10- to 30-fold higher elastase activity than did the fibroblasts. Three separate elastinolytic activities were observed in the tumor cell lines, and partial purification was achieved. The effect of steroid hormones on these elastases was examined. No stimulation of activity was found with any of the hormones, in any combination. However, there was marked inhibition of elastase with estradiol, progesterone, and dexamethasone of the ZR75-1 cell line. This is the estrogen receptor positive line that is estrogen responsive. The corticosteroids also inhibited the elastases of the estrogen receptor positive, non-responder cell line ZR75-30. No effect was seen on the elastases of receptor negative cells ZR75-31A with any of the steroid hormones. Stimulation of elastinolytic activities in these tumor cells must occur by some as yet unidentified pathway.
D001943:Breast Neoplasms / Q000201:enzymology*; D002460:Cell Line; D003546:Cysteine Endopeptidases; D004549:Elastin / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D012697:Serine Endopeptidases
D006728:Hormones; D004549:Elastin; D010450:Endopeptidases; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases