For the past ten years, our research has been focused on elucidating the mechanism by which procathepsin D (pCD) impacts cancer development. Various studies have shown that pCD is overexpressed and secreted by numerous cancer cell lines. After secretion, it exhibits “growth hormone-like” activity on cancerous cells but the exact mechanism of this mitogenic activity is not yet understood. The activation peptide of pCD (APpCD) (which is cleaved off upon activation of the zymogen) is responsible for the mitogenic function of pCD. Variousin vitro andin vivo studies support our theory that the APpCD interacts with both parent and neighborhood cancer cells and thus functions as an autocrine mitogen. We propose a model of pCD mitogenic function and also some possible approaches for treatment and prevention of certain types of cancer.
KeywordsBreast Cancer Breast Cancer Cell Human Breast Cancer Cell Line Activation Peptide Mitogenic Activity
activation peptide of pCD
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- Fusek M., Větvička V.:Aspartic Proteinases: Physiology and Pathology. CRC Press, Boca Raton 1995.Google Scholar
- Koelsch G., Metcalf P., Větvička V., Fusek M., p. 273 inAspartic Proteinases: Structure, Function, Biology, and Biomedical Implications (K. Takahashi, Ed.). Plenum Press, New York 1995.Google Scholar
- Nazeer T., Church K., Amato C., Ambros R.A., Rosano T.G., Malfetano J.H., Ross J.S.: Comparative quantitative immunohistochemical and immunoradiometric determinations of cathepsin D in endometrial adenocarcinoma: predictors of tumor aggressiveness.Modern Pathol. 7, 469–474 (1994).Google Scholar
- Schultz D.C., Bazel S., Wright L.M., Tucker S., Lange M.K., Tachovsky T., Longo S., Niedbala S., Alhadeff J.A.: Western blotting and enzymatic activity analysis of cathepsin D in breast tissue and sera of patients with breast cancer and benign breast disease and of normal controls.Cancer Res. 54, 48–54 (1994).PubMedGoogle Scholar
- Větvička V., Vagner J., Baudyš M., Tang J., Foundling S.I., Fusek M.: Human breast milk contains procathepsin-D detection by specific antibodies.Biochem.Mol.Biol.Internat. 30, 921–928 (1993).Google Scholar