Biological Function of Plasma Kallikrein in Mammary Gland Stromal Development and Tumor Metastasis; Final rept. 15 Feb 2005-14 Feb 2008

摘要

The plasminogen cascade of serine proteases has been affiliated in the mammary gland with both development and tumorigenesis. We have found that the dominant plasminogen activator during mammary gland stromal involution is plasma kallikrein (PKal), and that active PK appears in connective tissue-type mast cells in the mammary stroma during different phases of development. Examination of the extrahepatic expression of PKal has shown that PKal message is present in the mammary gland, and that increased expression levels correlate to periods of stromal remodeling. Additionally, an inhibitor of PKal that has been demonstrated to diminish mammary gland involution may be used to characterize PKal expression in the mammary gland as well as to identify targets of PKal activity during involution. Furthermore, mast cells are required for normal mammary duct branching morphogenesis during puberty. Lastly, attempts to produce a PKal knockout mouse were unsuccessful.