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)

3,3',4,4'-Tetrachlorobiphenyl (tetraCB) binds to the aryl hydrocarbon receptor (AhR), and several reports have demonstrated that AhR agonists exhibit antiestrogenic and antitumorigenic activities in human breast cancer cells, the rodent uterus and breast. In contrast, a recent study showed that 3,3',4,4'-tetraCB bound the estrogen receptor (ER) and exhibited ER agonist activities, and we therefore have reinvestigated the estrogenic and antiestrogenic activities of 3,3',4,4'-tetraCB. Our results showed that 3,3',4,4'tetraCB and a structurally related analog, 3,3',4,4',5-pentaCB, did not bind the mouse uterine or human ER, did not induce proliferation of MCF-7 or T47D human breast cancer cells or induce reporter gene activity in cells transfected with E2-responsive constructs derived from the creatine kinase B (pCKB) or cathepsin D (pCD) gene promoters. Moreover, 3,3',4,4'-tetraCB and 3,3',4,4',5-pentaCB did not induce an increase in uterine wet weight, peroxidase activity or progesterone receptor binding in the 21-25-day-old female B6C3F1 mouse uterus. In contrast, both compounds inhibited 17beta-estradiol (E2)-induced cell proliferation and transactivation in MCF-7/T47D cells and uterine responses in B6C3F1 mice; surprisingly inhibition of E2-induced reporter gene activity was not observed in T47D cells transfected with pCKB, and this was observed as a cell-specific response with other AhR agonists. Additionally, 3,3',4,4'-tetraCB significantly inhibited mammary tumor growth in female Sprague-Dawley rats initiated with 7,12-dimethylbenzanthracene. Our results indicate that 3,3',4,4'-tetraCB does not exhibit ER agonist activity but exhibits a broad spectrum of antiestrogenic responses consistent with ligand-mediated AhR-ER crosstalk.
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PMID:3,3'4,4'-Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity in the rodent uterus and mammary cells and in human breast cancer cells. 993 58

The enzyme poly(A) polymerase (PAP) catalyses the polyadenylation of mRNA and its activity levels vary within the cell cycle. The levels of activity of this enzyme were measured in the cytosol of breast tumours from 62 untreated patients and compared to clinical prognostic parameters as well as other biological markers. The enzyme levels measured ranged from 3 to 46 units/mg protein. A statistically significant association was observed between high PAP activity values and the TNM stage of the disease as well as node invasiveness. Furthermore, there was a positive correlation between PAP activity values and c-erbB-2 overexpression but not with its amplification. No significant correlation was observed with c-myc amplification or overexpression and cathepsin D levels. A direct relationship between steroid receptor content and PAP activity levels, which was more prominent in the case of the progesterone receptor, was observed. However, also on the basis of previous data PAP activity may prove to be indicative of aggressive disease. Furthermore, measurements of PAP activity may contribute to the definition of the biological profile of tumour cells.
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PMID:Poly(A)polymerase activity levels in breast tumour cytosols. 1008 76

The study of several human estrogen receptor positive breast cancer cell lines has allowed characterization of a number of estrogen-induced proteins (e.g. progesterone receptor, cathepsin D, pS2 and fibulin-1 in ovarian cell lines). In primary tumours, these markers have different prognostic significance for predicting whether the tumour will be hormone responsive (e.g. pS2, estrogen and progesterone receptors) or will develop metastasis (e.g. cathepsin D). Studies of estrogen-regulated genes should also lead to new therapeutic approaches for hormone-resistant cancers. The role of estrogens as mitogens stimulating the growth of breast and ovarian cancer cell lines is well established. By contrast, their action on metastasis appears more ambiguous. Breast cancer cells without estrogen receptor (ER) are generally less differentiated and more aggressive than those containing functional ER. Moreover, the reexpression of ER by transfection in ER-negative cell lines inhibit their metastatic and invasive potential. These results suggest a protective role of ER in tumor progression. Studies of the underlying mechanisms of this effect may open new therapeutical strategies.
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PMID:[Estrogen-induced genes in breast cancer, and their medical importance]. 1046

We previously reported that a 660-bp sequence that is homologous to the env gene of the mouse mammary tumor virus (MMTV) but not to endogenous retroviruses or to other known genes was present in 38% of human breast cancers and in some breast cancer cell lines studied (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995). Here, we have investigated whether the MMTV-like sequences were associated with the clinical, pathological, and molecular parameters that have been reported to define two subsets of human breast cancers. Archival breast carcinoma samples were analyzed for four clinical parameters, obtained from patients' records, and for six pathological characteristics. Expression of c-erbB-2, p53, bcl-2, progesterone receptor, laminin receptor, and cathepsin D was detected by immunochemistry using monoclonal antibodies. PCRs were used to amplify 250 bp of the MMTV env gene-like sequence. The chi2, log-rank, and generalized Wilcoxon tests were used to analyze the data. The MMTV env gene-like sequence was detected in 37.7% of the samples. The presence of this sequence was not significantly associated with any of the pathological clinical or biological parameters studied. It did correlate, however, with expression of the laminin receptor, a marker for invasiveness and poor prognosis. This is the first phenotypic characterization of human breast cancers containing retroviral sequences.
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PMID:Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor. 1047 94

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.
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PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

Lysosomal proteinases play an important role in the turnover of intracellular proteins, and acidic proteinases such as cathepsin D are known to be increased in breast carcinoma. In the present study the activity of a newly discovered acidic lysosomal pepstatin-insensitive proteinase (CLN2p) was measured in breast tissues by the most sensitive and highly specific assay that we had developed for the diagnosis of late-infantile neuronal ceroid lipofuscinosis (LINCL) (2). Samples from eight normal subjects undergoing reductive mammoplasty and 200 patients with primary breast carcinoma were analyzed. The results suggest a two- to seventeen-fold higher CLN2p activity in tumors, which was significantly and positively correlated with already known breast cancer biomarkers such as levels of cathepsin D, estrogen receptor and progesterone receptor. These results suggest a diagnostic and prognostic potential for this novel acid proteinase in breast cancer.
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PMID:A lysosomal pepstatin-insensitive proteinase as a novel biomarker for breast carcinoma. 1088 85

We assayed thymidine kinase (TK) and cathepsin D (Cath-D) in 200 breast carcinomas and we found that they were significantly correlated. This correlation was present in lymph node positive tumours, in G2 and G3, in T1 and in invasive ductal carcinomas. In addition, TK and Cath-D did not correlate with oestrogen receptor (ER) and progesterone receptor (PgR) status. We conclude that the relationship between Cath-D and TK may indicate a tumour population of high proliferation activity and invasiveness potential, related to a more aggressive phenotype, whose identification may be useful in defining prognosis.
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PMID:Co-expression of thymidine kinase and cathepsin D in 200 primary breast carcinomas. 1109 79

In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.
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PMID:Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients. 1128 57

Breast cancer screening is important for the early detection of breast cancer. Tumors that become symptomatic in the screening interval are known as interval cancers but the reasons for their rapid progression are unknown. Estrogen receptor expression is lower in interval cancers suggesting that they may have reduced hormonal responsiveness. To investigate this hypothesis we have measured the expression of the estrogen receptor and three estrogen-responsive genes (cathepsin D, progesterone receptor, and TFF1) in screen-detected and interval breast cancers. The expression of the protease cathepsin D was not associated with estrogen receptor in either group of tumor. Progesterone receptor expression was highly correlated with that of the estrogen receptor in both groups of tumors but it was not expressed at significantly different levels in the two groups of tumors. Expression of TFF1, a cellular motogen, was correlated with estrogen receptor in screen-detected but not interval cancers and was expressed at markedly higher levels in interval breast tumors, the group that expresses lower levels of estrogen receptor. Interval cancers are characterized by high levels of expression of TFF1 and/or Ki67 suggesting that cell migration and cell division play important roles in the rapid progression of interval cancers. The observation that TFF1 expression in interval cancers tends to be estrogen-independent and that interval cancers have reduced estrogen receptor expression suggests they may have a reduced response to hormone therapy.
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PMID:High expression of the trefoil protein TFF1 in interval breast cancers. 1143 68

In a total of 77 patients with epithelial ovarian carcinomas, new biologic parameters [estrogen and progesterone receptor (ER, PR), DNA-ploidy (DP), S-phase fraction (Spf), cycling index (Ki67), Her2b/neu oncoprotein, epidermal growth factor receptor (EGF-R), cathepsin D and P170 glycoprotein] have been simultaneously detected and correlated to the clinical outcome [progression-free (PFI) and overall survival (OAS)] in a preliminary study. Apart from conventional prognosticators (age, stage, grade, residual tumor) and the postoperative serum marker Ca125, DP (P = 0.01), Spf (P = 0.009), Ki67 (P = 0.05) and PR (P = 0.01) could predict a short OAS (log rank test), whereas cathepsin D was of borderline significance only. Prognostic significance could be improved by using combinations of different factors [two markers of differentiation (DP, PR), one marker of proliferation (Spf) and one marker describing local tumor spread (cathepsin D)]. The difference in prognosis between patients with either all or three favorable tumor factors and patients with two to four unfavorable tumor factors reached a similar significance as can be obtained using FIGO stage as a prognostic factor (P = 0.007 for PFI, P = 0.0005 for OAS). These results were similar if early stages (FIGO I and II) were excluded. However, in a Cox regression analysis, including stage and residual tumor, this combination was significantly independent for PFI and OAS and could give additional information. Therefore, the large number of new biologic tumor markers could be restricted to only a few significant prognosticators to predict prognosis in primary epithelial ovarian carcinoma. In the future tumor characterizations may allow more individualized treatment with more aggressive, or even without, cytotoxic therapy after primary surgery.
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PMID:Combination of new biologic parameters as a prognostic index in epithelial ovarian carcinoma. 1157 53


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