Cathepsin-D and its Role in Oncogenesis
aDepartment of Biochemistry and Microbiology and Center for Integrated Genomics, Faculty of Chemical Technology, Institute of Chemical Technology, Prague, bSigma-Aldrich Ltd., Prague
Cathepsin D (CD) is involved in oncogenesis particularly in the formation of breast tumors. The mechanism of its contribution to the process remains to be elucidated. Expression of cathepsin D is stimulated by estrogen in mammary cancer cells. It is also known that CD is very actively secreted from the breast tumor cells. It has been suggested that its oncogenic role might be related to its proteolytic activity and degradation of a certain tumor suppressor or to proteolytic destruction of a complex of the growth factor with its binding protein. The released growth factor may subsequently interact with its own receptor and activate cell proliferation. Some experimental data show that the activation peptide, proteolytically released from procathepsin during its activation, may be responsible for the mitogenic activity of procathepsin D (pCD). On the contrary, some data suggest that CD secreted by prostate cancer cells stimulates the formation of angiostatine and thus prevents nutrition of the growing tumor. Such function of CD is severely decreased in the case of pCD that is secreted by breast cancer cells probably due to different glycosylation of the CD forms. This review evaluates the current opinion on the role of pCD and the activation peptide in the carcinogenesis.
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