We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.
Clinical studies using both immunohistochemistry and immunoenzymatic assay of breast cancer cytosol have shown that the concentration of total cellular cathepsin D (52K + 48K + 34K) is related to the proliferation of mammary ducts and to the prognosis of breast cancer.
This difference, in addition to others concerning tissue distribution, mitogenic activity and hormonal regulation, strongly suggests that the 52-kD cathepsin D-like enzyme of breast cancer cells is different from previously described cathepsin D(s).
The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.
OHTam was more effective than E2 in increasing cathepsin-D mRNA levels, supporting the idea that anti-estrogen-resistant breast cancer continues to overexpress cathepsin-D.
In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer.
Overexpression of cathepsin D (CD), a ubiquitous lysosomal protease, is closely associated with a poor clinical outcome for patients with breast cancer.
C-myc and c-erbB-2 amplification and/or overexpression as well as total cathepsin-D (CD) concentration have been reported to be associated with poor prognosis in breast cancer.
17beta-estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast cancer cells and this response is inhibited by aryl hydrocarbon receptor (AhR) agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Our overall results provide the first evidence on the essential role of cathepsin-D in breast cancer, and support the development of a new cathepsin-D-targeted therapy.
Hypersecretion of the precursor of the lysosomal protease cathepsin D (procathepsin D) has been implicated in the invasive phenotype of human breast cancer.
Breast cancer incidence increases with age but this relationship has not been fully explored with regard to expression of estrogen receptor (ER) and ER-inducible genes (PR, pS2, Bcl2, cathepsin D), or the age-dependence of oxidant stress markers that also affect ER-inducible gene expression.
For example, E2 did not activate pCD in HepG2 cells transfected with wild-type or variant ER alpha, whereas E2 activated reporter gene activity in the four endometrial and breast cancer cell lines transfected with ER alpha and pCD, pCKB or pC3.
Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21).
Validated assays in the primary tumor of molecular markers such as ER, HER2-Neu and cathepsin D should help to predict which targeted therapy should be applied to cure breast cancer patients.
Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer.
Our studies also reveal that breast cancer cells, which are devoid of Maspin, are refractory to IFN-gamma with respect to changes in vacuolar pH and CatD.