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)

Matrigel invasion assays were used to characterize the invasive abilities of five breast cancer cell lines. Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to detect the differential gene expression of estrogen receptor (ER), E-cadherin, vimentin and cathepsin D in these cell lines. Using mRNA differential display, we identified novel cDNA clones representing the partial sequences of genes overexpressed in the invasive MDA-MB-435 cells as compared to that of the less invasive MCF-7 cells. One of the cDNAs was homologous to reticulocalbin. The studies were repeated in all of the cell lines and the overexpression of this cDNA was confirmed by RT-PRC and Northern hybridization analysis. Reticulocalbin was expressed in the highly invasive breast cancer cell lines but was not expressed in poorly invasive ones. Although its function is still unknown, reticulocalbin is implicated in tumor cell invasiveness because of its differential expression in breast tumor cell lines.
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PMID:Differential display of reticulocalbin in the highly invasive cell line, MDA-MB-435, versus the poorly invasive cell line, MCF-7. 907 Feb 64

The reduction of E-cadherin expression, which is involved in the initial step of invasion and metastasis of cancer, was investigated in 218 human breast carcinomas. Quantitative immunohistochemical assays (ICAs) were performed on frozen sections. Quantitation was assessed by processing digitized microscopic images of immunoreactions using a computerized system of image analysis (SAMBA). The results were correlated with clinicopathological data and quantitative immunodetection of other molecules. E-cadherin expression was significantly (P < 0.001) stronger in ductal carcinomas than in lobular carcinomas and stronger (P < 0.01) in low grades than in high grades, but E-cadherin was independent of lymph node status and tumour size. Also an inverse significant (P < 0.01) relationship was observed between E-cadherin expression on tissue sections and positive immunoreactions with anti-P53, MIB1 (growth fraction), and anti-c-erb-B2 product. Conversely, strong positive and anti-E-cadherin immunoreactions correlated with strong positive anti-ER and anti-PR immunoreactions (P < 0.01). No relationship was observed between E-cadherin and the results of quantitative ICAs of cathepsin D, CD31, and P-glycoprotein, assessed on consecutive sections from the same frozen tissue samples. The results show that preserved E-cadherin expression correlates with high degree of tumour differentiation, low proliferative activity, and low expression of prognostic markers. The deregulation of E-cadherin is independent of other steps of tumour invasion, such as protease digestion of extracellular matrix and angiogenesis.
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PMID:E-cadherin quantitative immunocytochemical assays in breast carcinomas. 915 15

Tumor metastasis is the main cause of mortality and treatment failure in cancer patients. It is a complex biological process regulated by alternations in expression of many genes. The p53 tumor suppressor gene has been shown to regulate expression of some metastasis-related genes. p53 transcriptionally activates expression of the genes encoding epidermal growth factor receptor, matrix metalloproteinase (MMP)-2, cathepsin D, and thrombospondin-1 but represses expression of the genes encoding basic fibroblast growth factor and multidrug resistance-1. Decreased expression of E-cadherin is associated with p53 alternations. Because these p53-regulatory genes either promote or inhibit tumor metastasis, the net effect of p53 expression on tumor metastasis depends upon the pattern of expression of these genes in a particular tumor. Because radiotherapy has been shown to increase tumor metastasis in both animal and human studies and because p53 is activated by radiation or DNA-damaging reagents, here we propose the working hypothesis that p53 may promote tumor metastasis upon induction by local radiotherapy or chemotherapy in some tumor types. For patients whose tumors contain wild-type p53, MMP inhibitors might be given with or before radiotherapy or chemotherapy to prevent an increase in tumor metastasis. Special caution should be taken with patients with cancers such as nasopharyngeal carcinoma in which p53 mutation is infrequent and radiotherapy is the main choice of treatment. To test our hypothesis, three studies are proposed and could serve as an initial step in understanding the complex biological process following radiation-induced p53 activation and its roles in regulation of tumor metastasis.
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PMID:Regulation of metastasis-related gene expression by p53: a potential clinical implication. 1002 7

Internalization of Listeria monocytogenes into non-phagocytic cells is mediated by the interactions between the two bacterial invasion proteins InlA (internalin) and InlB and their cellular surface receptors E-cadherin and c-Met. To get an insight into all the cellular components necessary for uptake and early intracellular life, we undertook a global proteomic characterization of the early listerial phagosome in the human epithelial cell line LoVo. First, we proceeded to an immunocytochemical characterization of intracellular marker recruitment to phagosomes containing latex beads coated with InlA or InlB. E-cadherin and c-Met were, as expected, rapidly recruited to the phagosomal formation site. Phagosomes subsequently acquired the early endosomal antigen 1 (EEA1) and the lysosomal-associated membrane protein 1 (LAMP1), while presenting a more delayed enrichment of the lysosomal hydrolase cathepsin D. Early phagosomes devoid of lysosomal, endoplasmic reticulum and Golgi enzymatic activities could then be isolated by subcellular fractionation of LoVo cells. Two-dimensional gel electrophoresis (2DPAGE) revealed differences between the protein profiles of InlA- or InlB-phagosomes and those of early/late endosomes or lysosomes of naive LoVo cells. One major protein specifically recruited on the InlB-phagosomes was identified by mass spectrometry as MSF, a previously reported member of the septin family of GTPases. MSF forms filaments that co-localize with the actin cytoskeleton in resting cells and it is recruited to the entry site of InlB-coated beads. These results suggest that MSF is a putative effector of the InlB-mediated internalization of L. monocytogenes into host cells.
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PMID:Distinct protein patterns associated with Listeria monocytogenes InlA- or InlB-phagosomes. 1189 66

Cancer invasion and metastasis develop through a sequence of processes involving loss of cell-cell and cell-matrix adhesions, proteolysis and induction of angiogenesis. We reviewed the current literature on the molecules that have been shown to play a significant role in these three steps of metastatisation in bladder cancer (BC) cells and their host microenvironment. Particular emphasis was given to markers that are assessable through immunohistochemistry and for which an additional prognostic value over the TNM variables has been recognized, in order to identify a subset of tumour markers readily available for application in daily clinical practice. We conclude that markers such as E-cadherin, Sialosyl-LeX, laminin, collagen IV, TSP-1 and MVD are useful prognostic markers, alpha, beta, and gamma catenin, MMP-2 and -9, uPAR, PD-ECGF and Bfgf can be considered potentially useful, while research on CD44, MMP-1 and -3, uPA, cathepsin D and VEGF has proved inconclusive. Further research in this field should concentrate on the molecules listed in the first group.
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PMID:Metastasis markers in bladder cancer: a review of the literature and clinical considerations. 1530 99

Meningothelial hyperplasia is a poorly characterized entity, often associated with advanced age, chronic renal failure, trauma, hemorrhage, and neoplasia. In order to elucidate the nature of this lesion, 11 cases defined by the presence of nests of 10 or more cell layers thick, were compared with normal arachnoidal cap cells and meningiomas. Immunohistochemistry and FISH were performed to determine NF2 (merlin), protein 4.1B, EMA, progesterone receptor (PR), EGFR, survivin, VEGF, PDGF-BB, PDGFR-beta, E-cadherin, and cathepsin D status. All cases had at least one putative predisposing factor, including hemorrhage (7), chronic renal disease (5), old age (5), trauma (1), and an adjacent optic nerve pilocytic astrocytoma (1). There was typically a discontinuous growth pattern, with no invasion of surrounding normal tissue. No gene deletions were found, though scattered polyploid cells were seen in 2 cases. The immunoprofile was similar to normal cap cells with one exception; whereas normal cells were uniformly negative for PR, nuclear positivity was seen in 64% of hyperplasias, a frequency similar to that of benign meningiomas. Our data suggest that meningothelial hyperplasia is a reactive process that is usually distinguishable from meningioma based on clinicopathologic and genetic features. It may be preneoplastic in some, though further studies are needed to test this hypothesis.
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PMID:Meningothelial hyperplasia: a detailed clinicopathologic, immunohistochemical and genetic study of 11 cases. 1591 82

Meningiomas are histologically and clinically diverse CNS neoplasms with few available immunohistochemical markers of differentiation and progression. Therefore, we investigated a panel of potentially useful meningioma-associated biomarkers using high throughput tissue microarray immunohistochemistry (TMA-IHC) with a TMA that includes 9 hemangiopericytomas (HPCs) and 41 meningiomas spanning all grades, as well as two subsets of atypical meningiomas, stratified according to clinical behavior. Antibodies utilized were progesterone receptor (PR), epithelial membrane antigen (EMA), cathepsin D, E-cadherin, platelet derived growth factor (PDGF) receptor beta, PDGF BB ligand, survivin, epithelial growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). In most cases, frequencies of tumor positivity were similar to those previously reported using whole section IHC. EMA, E-cadherin, and PDGFR-beta staining patterns distinguished the anaplastic meningiomas from the HPCs (P < 0.001, P = 0.02, P = 0.015, respectively). As in prior studies, PR and cathepsin D expression were inversely proportional to tumor grade. However, PR and EGFR were also differentially expressed between symptomatic, surgically resected benign meningiomas and incidental meningiomas found at autopsy. We conclude that (1) TMA-IHC is an accurate and efficient way to rapidly assess biomarkers in meningeal tumors, (2) EMA, E-cadherin, and PDGFR-beta are useful in distinguishing anaplastic meningiomas from HPCs, and (3) the expression patterns for incidental meningiomas differ slightly from their surgically resected symptomatic counterparts.
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PMID:High throughput screening of meningioma biomarkers using a tissue microarray. 1598 Sep 72

The development of novel proteomic technologies that will enable the discovery of disease specific biomarkers is essential in the clinical setting to facilitate early diagnosis and increase survivability rates. We are reporting a shotgun two-dimensional (2D) strong cationic exchange/reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (SCX/RPLC/ESI-MS/MS) protocol for the analysis of proteomic constituents in cancerous cells. The MCF7 breast cancer cell line was chosen as a model system. A series of optimization steps were performed to improve the LC/MS experimental setup, sample preparation, data acquisition and database search protocols, and a data filtering strategy was developed to enable confident identification of a large number of proteins and potential biomarkers. This research has resulted in the identification of >2000 proteins using multiple filtering and p-value sorting. Approximately 1600-1900 proteins had p < 0.001, and, of these, approximately 60% were matched by >or=2 unique peptides. Alternatively, >99% of the proteins identified by >or=2 unique peptides had p < 0.001. When searching the data against a reversed database of proteins, the rate of false positive identifications was 0.1% at the peptide level and 0.4% at the protein level. The typical reproducibility in detecting overlapping proteins across replicate runs exceeded 90% for proteins matched by >or=2 unique peptides. According to their biological function, approximately 200 proteins were involved in cancer-relevant cellular processes, and over 25 proteins were previously described in the literature as putative cancer biomarkers, as they were found to be differentially expressed between normal and cancerous cell states. Among these, biomarkers such PCNA, cathepsin D, E-cadherin, 14-3-3-sigma, antigen Ki-67, TP53RK, and calreticulin were identified. These data were generated by subjecting to MS analysis approximately 42 microg of sample, analyzing 16 SCX peptide fractions, and interpreting approximately 55,000 MS2 spectra. Total MS time required for analysis was 40 h.
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PMID:Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation. 1698 8

The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear particle-induced and septic loosening and to gather new insights into the pathogenesis of endoprosthesis loosening. Gene expression profiles were generated from five periprosthetic membranes of wear particle-induced and five of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n = 30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n = 54) or for other reasons, serving as control subjects (n = 259). Eight hundred twenty-four genes were differentially expressed with a fold change greater than 2 (data sets on http://www.ncbi.nlm.nih.gov/geo/ GSE 7103). Among these were chitinase 1, CD52, calpain 3, apolipoprotein, CD18, lysyl oxidase, cathepsin D, E-cadherin, VE-cadherin, nidogen, angiopoietin 1, and thrombospondin 2. Their differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear particle-induced prosthesis loosening (p = 0.001). However, chitinase activity as a marker for early diagnosis has a specificity of 83% and a sensitivity of 52%, due to a high variability both in the disease and in the control group.
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PMID:Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis? 1790 71

Molecular tools have increasingly been used for decision-making in patients with early breast cancer (EBC). Nevertheless, simple tools such as immunohistochemistry may still be required in particular cases to complement traditional and molecular prognosticators. In this study, the prognostic significance of three well-known immunohistochemical biomarkers, cathepsin D, E-cadherin and Ki67, was studied in 270 patients with EBC, followed by a median time of 126 months in a single institution. Histological examination was performed to confirm the histopathological diagnosis and select specimens. The specimens were evaluated using immunohistochemistry and survival curves were plotted. Results revealed the following patient characteristics: node-negative/1-3 lymph nodes in 228 (86%) patients, hormone receptor-positive in 217 (80%); triple-negative in 31 (11%), and Her2-overexpression in 23 (9%) patients. Breast cancer-related events occurred in 37 patients (14%). A total of 217 patients (80%) survived. Receiver operating characteristic analysis for breast cancer-specific survival showed an area under curve for the clinicopathological model of 0.75 (95% CI, 0.64-0.86), 0.79 (95% CI, 0.68-0.90) for the three-biomarker model, and 0.82 (95% CI, 0.72-0.92) for the E-cadherin and cathepsin D only model. We propose that a simple prognostic model based on combined scores of E-cadherin and cathepsin D may aid treatment decisions in patients with EBC.
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PMID:The prognostic importance of cathepsin D and E-cadherin in early breast cancer: A single-institution experience. 2284 86


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