Interestingly, mass spectrometry identified a cathepsin D protein single-nucleotide polymorphism (SNP) by alanine to valine replacement from the MCF-7 breast cancer cell line.
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.
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).
Cathepsin D, one of the attractive targets in the treatment of breast cancer, has been implicated in HIV neuropathogenesis with potential proteolytic effects on chemokines.
The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.
Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer.
Cathepsin D inhibitors as potential therapeutics for breast cancer treatment: Molecular docking and bioevaluation against triple-negative and triple-positive breast cancers.
Overexpression of cathepsin D (CD), a ubiquitous lysosomal protease, is closely associated with a poor clinical outcome for patients with breast cancer.
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.
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.
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.
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.
Because cathepsin D is a biomarker in aggressive forms of breast cancer and linked to poor prognosis, the effects of cathepsin D inhibition by 1 and 3 on the downstream cellular substrates cystatin C and PAI-1 were investigated.
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.
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.
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.
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).