Date of Award


Degree Type


Degree Name



Biological Sciences

First Advisor

Dufresne, M. J.


Biology, Cell.




The expression of the lysosomal cysteine proteases, cathepsins B, H, and L, and cysteine protease inhibitors in intracellular (cells) and extracellular (media) fractions prepared from the MCF-7 human breast cancer cell line, its adriamycin resistant variant, MCF-7/Adr$\sp{\rm R}$, and their somatic cell hybrid, M:A, was examined using synthetic substrates. Although these three cell populations had similar growth parameters, MCF-7/Adr$\sp{\rm R}$ demonstrated statistically significant 10-25 fold and 10-15 fold higher levels of intracellular cathepsins B and L activities respectively, than those found in the MCF-7 parent, or the M:A hybrid. Moreover, the increased levels of cathepsins B and L observed in MCF-7/Adr$\sp{\rm R}$ were not observed in either gpt or ras/gpt transfected MCF-7 cells. Cathepsin H activities were similar in all MCF-7 populations examined. The pattern of expression of acid/pepsin activatable cathepsin B in extracellular fractions of MCF-7, MCF-7/Adr$\sp{\rm R}$, and M:A was similar to that observed in intracellular fractions. Analysis of free and total cysteine protease inhibitor levels in MCF-7 and MCF-7/Adr$\sp{\rm R}$ cells using FPLC suggested MCF-7 cells possessed almost twice the total inhibitor level of MCF-7/Adr$\sp{\rm R}$, but retained better than half of this activity in a protease bound (ie., inactive) form. These results support the conclusion that alterations in the levels of total cysteine protease inhibitors, may contribute to increased levels of cathepsin B and L activity in MCF-7/Adr$\sp{\rm R}$ cells.Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1993 .S372. Source: Masters Abstracts International, Volume: 32-06, page: 1582. Adviser: Michael Dufresne. Thesis (M.Sc.)--University of Windsor (Canada), 1993.