Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Addition of estradiol-17beta in vitro to suspensions of isolated endometrial cells resulted in significant effects on glucose, water and electrolyte metabolism. Cells were prepared from uterine tissues of ovariectomized rats. In part, the procedures involved incubation with collagenase in Ca2+-, Mg2+-free, phosphate-buffered mammalian Ringer's solution, followed by restoration of divalent cations before gentle scraping of the endometrium from the underlying smoothmuscle. Cells were then disaggregated, washed, separated from coarse and fine debris, and incubated in an enriched medium for 2 h before the start of all experiments. Cellular integrity was established by measurement of electrolyte contents and by dye exclusion methods. Substantial production of 14CO2 from glucose-U-14C by the cell suspensions provided further evidence of cell viability. Estradiol-17beta, 10-9M, elicited significant increments in sodium and water contents within 2 h. Addition of estradiol-17beta, but not the alpha-epimer, also resulted in a significant increase in the yield of 14CO2 as early as 1.5 h, peaking at 2 h. The responses were dose-dependent between 10-10M through 10-8M. The stimulatory effect of estradiol-17beta at 10-9M was abolished in the presence of 3 times 10-6M cortisol or by cellular homogenization. Epithelial cells isolated from rat urinary bladder responded significantly to 6 times 10-9M aldosterone but not to estradiol-17beta, demonstrating specificity of the target site. These data lend further support to the suggestion that a primary action of estrogen in its target cell involves specific changes in the ionic and biochemical profile of the cytoplasm which may ultimately be communicated to the nucleus.
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PMID:Steroid hormone-responsive, isolated endometrial cells. 112 Apr 83

Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid-sensitive breast cancers; however, little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and -negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells. HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020 alone or in combination with estradiol, but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP-2. Interestingly, however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were 50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid-independent MDA-MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid-sensitive breast-cancer cell, leading to the acquisition of the metastatic phenotype.
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PMID:Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast-cancer cells. 139 48

The effect of ipriflavone (IP) on the proliferation and differentiation of rat osteoblast-like (ROB) cells and human periodontal ligament fibroblasts (HPLF) was studied in the presence and absence of estrogen. ROB cells were isolated from newborn rat calvaria by sequential collagenase digestion and HPLF from the outgrowth of human periodontal ligament in culture. The alkaline phosphatase (ALP) activity, employed as a marker of bone cell differentiation, was significantly enhanced by IP in both cell types; however, the concentration at which IP had a maximal effect was lower in ROB cells than in HPLF (10(-10) versus 10(-7) M, respectively). Cell proliferation judged by DNA content was either constant (ROB cells) or slightly increased (HPLF) by IP up to 10(-10) M, and decreased significantly above that concentration. In addition, the dose-dependent effect of estrogen on the growth and differentiation of each cell type in the presence and absence of IP was also tested. At the concentrations of IP which showed maximum effects in the induction of ALP, 10(-10) M for ROB cells and 10(-7) M for HPLF, IP inhibited DNA increase in an estrogen-independent manner. Estradiol (10(-11)-10(-9) M) itself increased the growth rate of both cell types significantly in a dose-dependent manner. Regardless of the concentrations of estradiol tested, ALP activities of both ROB cells and HPLF were elevated by the addition of IP. The ratio of ALP in the presence and absence of IP was similar over the range of estradiol concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ipriflavone and estrogen on the differentiation and proliferation of osteogenic cells. 142 78

An animal model for studying tumor dormancy was established by two-way selection of tumor-progressive and nonprogressive (tumor-dormant state) ddY mice in the same basal stock. In the tumor-progressive (prg) substrain of mice, Ehrlich ascites tumor cells (2 x 10(7)) subcutaneously inoculated into the dorsal skin formed a progressive solid tumor. In the tumor-dormant substrain (drm) of mice, the same tumor cells did not grow at all but formed a small caked nodule (1 to 3 mm in diameter) within 1 week. Some of the tumor cells persisted in the nodule at least 3 months without apparent mitotic figures. Such dormant tumor cells emerged and revealed outgrowth to overt solid tumors after they were transplanted into the dorsal skin of prg mice or into athymic mice (C57BL/6J nu/nu). To estimate the predisposition of drm mice to form tumors, the effect of certain drugs on the tumor-dormant state was examined. Estradiol, progesterone, dexamethasone, prostaglandin E2, Cyclosporin A, and collagenase all failed to promote the emergence of dormant tumor cells in drm mice.
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PMID:Tumor dormancy and the effect of selected drugs on the tumor-dormant state. 147 6

The present study determined whether a developmental increase in placental low density lipoprotein (LDL) uptake occurred in baboon pregnancy, which was related to the increasing concentrations of estrogen typical of advancing gestation. LDL uptake was determined on collagenase-dispersed placental trophoblast cells purified via 50% Percoll gradient centrifugation and obtained from baboons between days 55-178 of gestation (i.e. the last two-thirds of gestation; term = 184 days). The majority of cells in the 50% Percoll-isolated fraction used to determine LDL uptake were syncytiotrophoblasts at all stages of gestation examined, as determined by immunohistochemical staining for syncytiotrophoblast-specific placental lactogen and pregnancy-specific-beta 1-glycoprotein. Placental LDL uptake, as determined by Scatchard analysis, increased progressively during the last two-thirds of gestation and was correlated (r = 0.87, P less than 0.001; curvilinear regression) with gestational age. Mean +/- SE LDL uptake early in pregnancy on days 55-58 was 1.9 +/- 0.2 ng/micrograms cell protein (n = 3). Placental LDL uptake (ng/microgram cell protein) at midgestation on days 94-104 (2.8 +/- 0.2; n = 5) increased to a value late in gestation on days 159-178 (14.6 +/- 1.0; n = 13), which was approximately 5-fold greater (P less than 0.001) than at midgestation, whereas uptake on days 128-138 was intermediate in value (8.3; n = 2) between the latter two periods. The apparent dissociation constant for placental LDL uptake was lower (P less than 0.01) at midgestation (0.33 micrograms/ml) than late in gestation (0.81 micrograms/ml). Placental LDL degradation, which depends on uptake, also increased with advancing stages of pregnancy, and was correlated (r = 0.74, P less than 0.01; curvilinear regression) with gestational age. Overall mean peripheral serum LDL cholesterol concentration was 46.5 +/- 1.7 mg/dl between days 50-170 of gestation. However, there was no significant change in serum LDL levels during this period. Maternal peripheral serum estradiol concentrations increased from 0.3 ng/ml on day 55 to an initial peak of approximately 3.5 ng/ml on days 70-80, then declined to approximately 1.0 ng/ml at midgestation. Estradiol then increased progressively throughout the remainder of pregnancy to maximal values of over 6 ng/ml late in gestation. In summary, there was a progressive increase in placental LDL uptake with advancing stages in the last two-thirds of baboon pregnancy, which was associated with a concomitant rise in maternal serum estradiol concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental increase in placental low density lipoprotein uptake during baboon pregnancy. 153 17

Cervical ripening is reviewed from the viewpoint of mechanical properties, histological and biochemical structure of cervical tissue, and the role of hormones and other bioactive agents in the process. The uterine cervix begins abruptly with a 2-3 mm transition from the myometrium and is made of 80% type I collagen and 20% type III collagen fibers covalently cross linked, and glycosaminoglyucans covalently bound to protein cores. During pregnancy the collagen concentration is halved and its extractability increases due to changes in the proteoglycan composition, an increase in acidic relative to neutral proteins. These changes are responsible for the softening of the cervix (Goodell's sign) and the isthmus (Hegar's sign). Histologically the collagen fibers appear thinner and more spread out. Polymorphonuclear leukocytes and eosinophils may be involved in the softening process. Factors theorized or know to be involved in cervical ripening are progesterone, estradiol, prostaglandins (PGs), relaxin, and cytokines. Progesterone withdrawal has been shown in animal models. Estradiol either induces PG synthesis or sensitizes the cervix to locally produced PGs. PGE2 and PGF2alpha receptors have been found in cervical plasma membranes, have been isolated from tissue, their local synthesis can be manipulated, and their clinical use is well documented. Relaxin is a peptide synthesized in the corpus luteum, uterus and placenta, and is known to relax the pelvic girdle, restrain myometrial activity and soften the cervix. Cytokines such as interleukin-1 and tumor necrosis factor are being studies because of their ability to stimulate collagenase.
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PMID:The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs. 222 99

A reproducible cell culture system is described that allows the study of adipose conversion in fibroblast-like cells isolated by collagenase digestion of epididymal and perirenal adipose tissue from male rats weighing 70-200 g. Adipose conversion as measured by lipid accumulation and increase in glycerophosphate dehydrogenase (GPDH) activity during differentiation strongly depends on the density at which cells are inoculated and starts only when cells are confluent and when physiological amounts of corticosterone and insulin are added. beta-Estradiol, testosterone, thyroxine, triiodothyronine, and growth hormone do not affect the differentiation process. Methylisobutylxanthine added during the first 2 days after confluence, added with insulin and corticosterone, potentiates the effect of insulin on GPDH activity and accelerates triglyceride accumulation. The effect of methyl-isobutylxanthine seems to be mediated by increased cyclic AMP concentrations, inasmuch as it may be replaced by forskolin.
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PMID:Hormonal regulation of the differentiation of rat adipocyte precursor cells in primary culture. 244 Sep 70

Cervical tissue from ewes at various stages of pregnancy was examined for evidence that collagenase is involved in the process of cervical softening. Collagenase activity was detected in medium after 2-3 days culture of ovine cervical explants, but there was no significant difference in total enzymic activity produced by explants from non-pregnant, early pregnant or late pregnant animals when expressed as units/mg wet weight of tissue over five days in culture. Oestradiol infusion into ewes prior to parturition did not alter the enzyme activity subsequently produced in explant culture. However, the DNA concentration, and hence the number of cells per unit volume, decreased significantly with length of pregnancy, this effect being due to expansion of cervical tissue which occurs late in pregnancy. Thus, if collagenase activity is expressed relative to DNA and hence cell number, there is evidence for increased production per cell in order to keep the tissue concentration constant. However, as the concentration of collagen in cervix remains constant during pregnancy, the ratio of collagenase activity to collagen is also constant. It is therefore concluded that there is no evidence of a role for increased collagenase activity in cervical softening in the ewe.
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PMID:Increased collagenase activity is not detectable in cervical softening in the ewe. 285 Jan 33

The present study determined if estrogen modulates the responsivity of the adrenal gland of the baboon fetus to tropic hormones such as adrenocorticotropic hormone and prolactin. Adrenal glands were obtained from seven baboon fetuses at midgestation (days 100 to 105). Adrenal cells were dispersed in medium 199 with 0.2% collagenase for 10 minutes at 37 degrees C. Approximately 10(5) cells/4.0 ml of medium 199 were incubated for 24 hours at 37 degrees C with 10 nmol of adrenocorticotropic hormone or 10 nmol of ovine prolactin in the presence or absence of 10(-5) or 10(-6) mol/L of estradiol. The major steroid formed and secreted into the medium was dehydroepiandrosterone. Mean +/- standard error basal formation of dehydroepiandrosterone was 176 +/- 64 ng/10(5) cells/24 hours. Dehydroepiandrosterone formation was increased (p less than 0.05) 3.5-fold and five-fold by adrenocorticotropic hormone and prolactin, respectively. Estradiol at 10(-5) mol/L prevented the response in dehydroepiandrosterone obtained with adrenocorticotropic hormone alone. Estradiol alone had no effect on dehydroepiandrosterone. The results suggest that estrogen modulates the regulatory effects of adrenocorticotropic hormone on dehydroepiandrosterone formation by the adrenal gland of the baboon fetus.
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PMID:Effect of estrogen on dehydroepiandrosterone formation by baboon fetal adrenal cells in vitro. 303 61


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