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Cyst fluid proteases.

L Kesner1, W S Yu, H L Bradlow

  • 1Department of Biochemistry, State University of New York Health Science Center, Brooklyn 11203.

Annals of the New York Academy of Sciences
|January 1, 1990
PubMed
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Breast cyst fluid origin is unclear, but protease activity imbalance may drive gross cystic disease. This imbalance could link to breast cancer risk in affected women.

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Biology

Background:

  • The origin of breast cyst fluid is not fully understood.
  • Two types of breast cysts exist: Type I (high K/Na ratio, secretory) and Type II (high Na/K ratio, potentially transudative from plasma).
  • An imbalance between proteases and protease inhibitors in cyst fluid may contribute to the pathogenesis of breast gross cystic disease.

Purpose of the Study:

  • To investigate the role of protease activity and its inhibitors in breast cyst fluid.
  • To characterize the major protease fraction in cyst fluid and its potential link to progesterone binding protein (GCDFP-24).
  • To explore the relationship between cyst fluid proteases, plasma protease inhibitors, and the potential involvement in breast cancer development.

Main Methods:

Related Experiment Videos

  • Analysis of cyst fluid composition, including Na/K ratios and protease activity.
  • Use of affinity chromatography with aprotinin or benzamidine ligands to isolate protease fractions.
  • Characterization of protease activity using 14C-labeled protein substrates and comparison with known proteases (trypsin, calpain).
  • Development of a semiquantitative method for estimating protease activity in cyst fluid using albumin-agarose gel plates.
  • Investigating the inhibitory capacity of human plasma on cyst fluid protease activity.

    • Main Results:

    • Breast cyst fluid contains active proteases, with variability in activity observed.
    • The major protease fraction in cyst fluid appears to be closely related to, or the same as, progesterone binding protein (GCDFP-24).
    • Human plasma contains inhibitors capable of significantly reducing cyst fluid protease activity, with a plasma/cyst fluid ratio of 6/1 found to be inhibitory.
    • Cyst fluid proteases exhibit a cleavage pattern distinct from trypsin and calpain.
    • Albumin concentration in cyst fluid may be low due to its role as a protease substrate.

    Conclusions:

    • An imbalance between proteases and protease inhibitors in breast cyst fluid is implicated in the pathogenesis of gross cystic disease.
    • The identified protease, potentially GCDFP-24, and its interaction with inhibitors warrant further investigation.
    • The findings suggest a potential link between breast gross cystic disease, protease activity imbalance, and an increased incidence of breast cancer.