Proprotein Convertases in Human Breast Cancer
Final rept. 1 Sep 1997-28 Feb 2001
MANITOBA UNIV WINNIPEG
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Proprotein convertases are members of a new class of endoproteolytic enzymes that are believed to play important roles in human neoplasia. Based on our previous detection of proprotein convertases in human breast tumors, the present study is designed to study the biological significance of these enzymes in breast development and cancer. Proprotein convertase gene transfections into MCF-7 human breast cancer cells led to profound changes in the breast cancer cells. MCF-7 cells that over-expressed proprotein convertases have become more dependent on estrogen for growth both in vitro and in vivo as tumors grown in athymic mice. As well, convertase-transfected breast cancer cells become more resistant to the anti-estrogen Tamoxifen. To further study the role of proprotein convertases in mammary gland development and tumorigenesis, transgenic mice bearing convertase transgenes targeted to the mammary gland have been generated. Preliminary studies have revealed phenotypic changes in the mammary glands of these novel transgenic mice, an observation that supports the hypothesis that elevated expression of proprotein convertases is an important determinant in the pathogenesis of the breast.
- Medicine and Medical Research