Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) growth in lymphocyte cultures was increased when the virus inoculum was incubated in breast milk. The enhancing effect of milk was abolished by anti-cathepsin D antibody or by pepstatin A, a cathepsin D inhibitor. The cathepsin D-producing CD4-negative MCF7 mammary cells supported the growth of some HIV-1 isolates. An MCF7 line chronically producing HIV-1 IIIb was obtained. Cathepsin D may induce conformational modification of viral gp120, allowing direct interaction with a coreceptor. We demonstrated the presence of CXCR4 mRNA in MCF7 cells.
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PMID:A human milk factor susceptible to cathepsin D inhibitors enhances human immunodeficiency virus type 1 infectivity and allows virus entry into a mammary epithelial cell line. 1062 64

In the process of metastasis, malignant cells are released from the primary tumor and migrate to specific organs via the lymphatic and blood circulation systems. These circulating tumor cells have been characterized by immunochemistry, the reverse transcription-polymerase chain reaction, and flow cytometry. Using the MCF-7 breast cancer cell line, we have developed a two-color ELISPOT assay to detect cells secreting cathepsin D protease and MUC1 glycoprotein, markers associated with the risk of metastases in breast cancer. The threshold of detection of this ELISPOT assay was one cathepsin D- or MUC1-secreting MCF7 cell per 5 ml of control blood. In 16 patients with breast carcinoma metastases, 1 to 1940 cathepsin D- or MUC1-secreting cells per 2x10(7) PBMC were enumerated, whereas none were found in 11 controls. Moreover, in six patients 6-60% of MUC1-secreting cells also expressed the CXCR4 chemokine receptor, which is involved in the homing of metastatic breast cancer cells. The ELISPOT assay described here allowed us to enumerate cathepsin D- and/or MUC1-secreting cells in the MCF-7 cell line and in the peripheral blood of patients with disseminated breast cancer. The combination of the ELISPOT assay and CXCR4-positive cell sorting identified subsets of MUC1-secreting cells in the peripheral blood of these patients.
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PMID:Characterization and enumeration of cells secreting tumor markers in the peripheral blood of breast cancer patients. 1591

Estrogen receptors (ERs) regulate the transcription of genes involved in breast cancer cell proliferation, invasion and metastasis. In addition to ligand concentration, phosphorylation and coactivator/corepressor levels control ER-dependent transcription. In this study, we used MCF-7 breast cancer sublines with variable levels of the steroid receptor coactivator 1 (SRC-1) to investigate the importance of coactivator levels in basal and estrogen-inducible expression of SDF-1alpha/CXCL12, cathepsin D and cMyc. Basal expression of SDF-1alpha and cMyc but not of cathepsin D was substantially lower in a MCF-7 subline lacking SRC-1 ((MCF-7/p2) compared with MCF-7 sublines expressing SRC-1 (MCF-7/p1 and LCC2). Although estrogen efficiently induced SDF-1alpha in MCF-7/p1 cells, very little induction of this gene was observed in MCF-7/p2 cells. The absence of SRC-1 had no effect on estrogen-inducible expression cMyc and cathepsin D suggesting that coactivator levels determine the expression of only a subset of estrogen-regulated genes. Introduction of SRC-1, SRC-2/TIF-2 or SRC-3/AIB1 increased basal expression of SDF-1alpha in MCF-7/p2 cells. Consistent with the role of SDF-1alpha in mediating estrogen-induced proliferation, estrogen failed to increase proliferation of MCF-7/p2 cells. In matrigel invasion assays, conditioned media from MCF-7/p1 but not MCF-7/p2 cells increased invasion of cancer cells expressing metastasis-associated genes and CXCR4, the receptor for SDF-1alpha. These results suggest that coactivators control SDF-1alpha expression, which mediates estrogen-induced proliferation and invasion through autocrine and paracrine mechanisms, respectively. These results also provide a molecular explanation for recent observations linking co-overexpression of coactivators and her2/neu with poor prognosis: coactivators increase SDF-1alpha expression whereas her2/neu stabilize CXCR4 protein.
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PMID:The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1alpha/CXCL12. 1591 9