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)

The in vitro degradation of microtubule-associated protein 2 (MAP-2) and tubulin by the lysosomal aspartyl endopeptidase cathepsin D was studied. MAP-2 was very sensitive to cathepsin D-induced hydrolysis in a relatively broad, acidic pH range (3.0-5.0). However, at a pH value of 5.5, cathepsin D-mediated hydrolysis of MAP-2 was significantly reduced and at pH 6.0 only a small amount of MAP-2 was degraded at 60 min. Interestingly, the two electrophoretic forms of MAP-2 showed different sensitivities to cathepsin D-induced degradation, with MAP-2b being significantly more resistant to hydrolysis than MAP-2a. To our knowledge, this is the first clear demonstration that MAP-2 is a substrate in vitro for cathepsin D. In contrast to MAP-2, tubulin was relatively resistant to cathepsin D-induced hydrolysis. At pH 3.5 and an enzyme-to-substrate ratio of 1: 20, only 35% of the tubulin was degraded by cathepsin D at 60 min. The cathepsin D-mediated hydrolysis of tubulin was optimal only at pH 4.5. These results demonstrate that MAP-2 and tubulin are unequally susceptible to degradation by cathepsin D. These data also imply a potential for rapid degradation of MAP-2 in vivo by cathepsin D either in lysosomes or perhaps autophagic vacuoles of the neuron.
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PMID:Proteolysis of microtubule-associated protein 2 and tubulin by cathepsin D. 191 74

We evaluated the intra- and inter-observer reproducibility of quantitative immunohistochemical (IHC) analyses using the Cell Analysis Systems (CAS) 200/486 image analyzer of Estrogen Receptor (ER), Progesterone Receptor (PR), proliferation-associated nuclear protein (Ki67), HER-2/neu (c-erbB-2) protein over-expression and cathepsin D (CD) in 20 randomly-selected invasive breast carcinomas. Qualitative analysis of IHC Epidermal Growth Factor Receptor (EGF-R) was also assessed in this study for comparative purposes. Duplicate blind assessments by the same observer showed excellent correlations for all quantitative IHC features (P < 0.001; P = 0.004 for neu). However, the immuno-quantitative analyses results between the 3 different operators showed lower correlation coefficient values, thus being less reproducible. This resulted in systematic differences and bias between the observers. This was also clear from the overall agreement between the 3 observers which was 70% for ER, 70% for PR, 56% for Ki67, 79% for c-erbB-2 and 75% for CD. The qualitative visual assessments of EGF-R, expressed as either positive or negative, showed a 75% agreement between observers and 85% intra-observer agreement (comparable to quantitative digital image processing results). The same results were obtained with kappa statistics. A further analysis of the factors causing the lack of reproducibility was performed. For quantitative IHC, segmentation of stored and retrieved digitized images was quite reproducible between and within well-trained observers. However, variation between different fields of vision of one and the same section showed large variations for most cases. Therefore, differences in sampling of fields within a section appeared to be the major cause of lack of reproducibility between observers, although segmentation differences still added slightly to the inter-observer variations. Accordingly, a strict sampling protocol of fields of vision is mandatory to obtain reproducible quantitative IHC results. It is clear from the present study that so-called random (but in fact, at convenience) selection of fields of vision for measurement is not a sufficient guarantee of adequacy of the sampling.
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PMID:Quantitative immunohistochemistry using the CAS 200/486 image analysis system in invasive breast carcinoma: a reproducibility study. 754 96

The mammary gland seems to be the only organ that is not fully developed at birth. Estrogens stimulate breast tissue via estrogen receptors (ERs). In the mammary gland, ER-mediated mechanisms have been shown to regulate: various growth factors, such as TGF-alpha and TGF-beta; enzymes, such as cathepsin D and plasminogen-activator; proto-oncogenes, such as c-fos, c-myc and HER-2/neu; cyclines and other regulatory substances that provide signaling systems for cell division and differentiation; other steroid receptors and epidermal growth factor receptors. Estrogen target genes contain estrogen-responsive elements. In these genes, transcription will be activated through interaction with the estrogen/ER protein complex. Subsequent activation of proto-oncogenes provides an explanation for the stimulating effect of estrogens on the glandular breast. Progesterone may be the key in influencing the risk of breast cancer with the peak of mitotic activity in the breast during the luteal phase of the menstrual cycle. On the other hand, in human breast cancer cell lines, both proliferation and inhibition have been observed with various progestational agents. Relevant biological and clinical issues are pregnancy and exposure to exogenous hormones. The intense hormonal stimulation of pregnancy (both estrogen and progesterone) has no adverse impact on the course of breast cancer. Pregnancy, with its mammogenetic differentiation, results in the protection of this organ from carcinogenesis. Characterization of specific lobular morphology serves as an indicator of the level of differentiation achieved by the organ, and thus provides means to assess the risk of the gland undergoing neoplastic transformation when exposed to given agents. Sufficient evidence exists to indicate the possibility of a slightly increased risk of breast cancer after approximately one decade of postmenopausal estrogen use. A review of the epidemiologic studies of postmenopausal hormone replacement and the risk of breast cancer fails to provide definitive evidence. Recent information derives from observations of cellular proliferation, plasma and tissue estradiol and progesterone receptor levels, and the percentage of apoptotic epithelial cells in human breast tissue. Several studies suggest that short-term, continuous combined HRT does not increase breast cancer recurrence or mortality. The participation of sexual hormones in the mammogenetic process during pregnancy might serve as an intermediate end point in assessing the effectiveness of hormones as chemopreventive agents. Investigations based on history, and breast morphology, should enable us to select estrogens and progestogens for HRT, and adopt optimal therapeutic regimens.
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PMID:Potential benefits of estrogens and progestogens on breast cancer. 992 May 36

Estrogen receptors, progesterone receptors, and cathepsin D were determined in 10 patients with giant-cell bone tumor. Progesterone receptors were expressed in 5 of 10 patients tested, whereas low levels of estrogen receptors were found in 1 patient. Cathepsin D levels were elevated in 5 of 5 samples studied. High values of progesterone receptors correlated with low tumor grade. Cathepsin D levels correlated negatively with tumor grade but positively with local tumor expansion. Giant-cell bone tumor expressing progesterone receptors may manifest benign behavior. Cathepsin D may be involved in tumor expansion, possibly through its effect on bone resorption.
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PMID:Giant-cell tumors of bone and progesterone receptors. 1469 Feb 91

Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of pancreatic cancers. CA19-9 is not widely used for screening PDAC due to its low sensitivity. Here, we studied the clinical usefulness of cathepsin D, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) for screening patients with PDAC. A total of 248 patients with PDAC and 216 control subjects were recruited (109 PDAC patients and 70 controls in the training set and 139 PDAC patients and 146 controls in the validation set). We measured serum levels of cathepsin D, TIMPs (-1, -3, and -4), and MMPs (-1, -7, -8, and -9) using Fluorokine MAP multiplex kits. The concentrations of cathepsin D and MMP-7 were significantly higher in PDAC subjects than control subjects. In the training set, the diagnostic sensitivity and AUC of the panel of CA19-9, cathepsin D, and MMP-7 for PDAC were increased to 88% and 0.900, compared to 74% and 0.835 of CA19-9 single marker at 80% specificity. The sensitivity using cut-off value of biomarker panel was significantly increased in the validation set as well as training set. Our findings indicate that a serum biomarker panel consisting of CA19-9, cathepsin D, and MMP-7 may provide the most effective screening test currently feasible for PDAC.
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PMID:Serum CA19-9, cathepsin D, and matrix metalloproteinase-7 as a diagnostic panel for pancreatic ductal adenocarcinoma. 2306 39