Molecular Characteristics of Multicorn, a New Large Proteolytic Assembly and Potential Anti-Cancer Drug Target, in Human Breast Cancer Cells
Annual rept. 1 May 2003-30 Apr 2004
TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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We showed that breast cancer MCF7 cells posses a distinct regulation of proteolysis executed by the multicorn when compared with non-cancerous MCF10A cells. The apparent lower total activity of the multicorn in MCF7 cells may constitute an important link between the overall efficiency of cell division and nuclear and cytosolic proteolysis. Regulation of the assembly of the large and small forms of multicorn is accomplished through phosphorylation of their subunits. On the basis of our data we suspect that multicorn constitutes an important player in cellular protein turnover and in regulation of cell cycle. Its distinct properties in the control and cancerous cells strongly suggest that the multicorn may represent an attractive drug target and a marker of physiological state of the cells. Since it has been suspected that both proteasome and the multicorn may share some of their functions, we tested the performance of cancerous and control cells treated with inhibitors of the proteasome, the multicorn, and both the inhibitors combined. We found that high doses of multicorn or proteasome inhibitors are toxic to the cells. However, we determined that a combination of low doses of both inhibitors effectively kills the cancerous cells allowing the non-cancerous cells to recover.
- Medicine and Medical Research