Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer cells are characterized by frequent occurrence of the DF 3 breast-cancer associated antigen in the cytoplasmic area. This study elucidated the details of this cytoplasmic reactivity by immunoelectron microscopy. In infiltrating breast carcinomas, the DF 3 antigen was localized in rough endoplasmic reticulum (rER), perinuclear space, Golgi complex, membrane-bound granules and along the outer surface of cell membrane. The antigen was also accumulated in the cytosol. In contrast to this, benign lesions showed localization of the DF 3 antigen mainly along the outer surface of apical cell membrane and rarely in rER or cytosol. The present study indicated that the DF 3 antigen was of secretory type and commonly localized on the outer surface of apical cell membrane in both malignant and benign lesions. Carcinoma tissues were further characterized by frequent occurrence of immunoreactivity related to the process of antigen synthesis. The diffuse cytosolic reactivity may be associated with disordered transportation of the antigen in the cytoplasm.
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PMID:Immunoelectron microscopic localization of DF 3 cancer-associated antigen in human breast cancer. 166 26

The evidence that estrogen protects against coronary heart disease is biologically plausible, consistent, and strong. These benefits have not been established by a randomized trial, however, so that the degree of protection against heart disease might have been overestimated because estrogen users tend to be healthier than nonusers. A randomized trial to determine whether estrogen alone or in combination with progestin protects against coronary heart disease should be given a high priority. Progestins generally attenuate the effects of estrogen on the concentrations of HDLC. It is not known whether this effect also limits the beneficial effects of estrogen on the risk of coronary heart disease. Recent studies suggest that estrogen may protect against coronary heart disease in other ways besides favorably altering serum concentrations of lipoproteins and that progestins might not have adverse effects on the risk of heart disease. Currently, theoretical concerns that progestins might be harmful seem outweighed by the evidence that they protect against endometrial cancer in women who have a uterus. For these women, some may find the side effects of progestins to be so bothersome that they prefer to take estrogen alone. This approach is reasonable so long as the patient has periodic endometrial biopsies for early detection of pre-malignant or malignant endometrial changes. Women without a uterus should take estrogen alone. Women who take long-term estrogen therapy appear to have about a 30% greater chance of developing breast cancer. On the other hand, breast cancer that develops while taking estrogen therapy might have a slightly better prognosis. Quantitative comparisons of fatal conditions suggest that the benefits of long-term therapy outweigh the risks. But these comparisons assume that all causes of deaths are equally important and do not adequately take account of other psychologic and physical effects of hormone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluating the benefits and risks of postmenopausal hormone therapy. 175 Apr 10

The anti-estrogen binding site (ABS) is an apparently ubiquitous component of cells that has been shown to be intimately linked with the antiproliferative effects of certain antiestrogenic compounds, like tamoxifen, which is currently used for the treatment of breast cancer. However, the identification and in vitro study of this novel protein has been hampered to date by a lack of convenient probes that will efficiently label the molecule in nonpurified preparations. Thus, using a selective ABS ligand (4-benzylphenoxy-N-ethylmorpholine, MBPE) as starting material, we synthesized a photosensitive azido derivative, [(2-azido-4-benzyl)phenoxy]N-ethylmorpholine (azido-MBPE) that can be prepared in a tritiated form. Azido-MBPE has a high affinity for ABS (Kd = 3 nM), identical to that of tamoxifen, and covalently labels 5 and 12% of membrane-bound and detergent-solubilized ABS, respectively. Its incorporation is selectively and competitively inhibited by other ABS ligands (tamoxifen greater than nitromifen greater than hydroxytamoxifen). [3H]Azido-MBPE potently photolabels either membrane-bound or detergent-solubilized ABS as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions revealing specific photoincorporation in a protein band of Mr = 40,000. This molecular weight is approximately two times lower than what we observed previously for ABS preparations studied under nondenaturing conditions and postlabeled with [3H]tamoxifen (Mr = 80,000-110,000). In chromatofocusing experiments with photolabeled ABS, a single specifically labeled protein fraction migrating with a pI of 6.4 was found to exhibit a Mr of 40,000 when subsequently electrophoresed on sodium dodecyl sulfate-polyacrylamide gels. These results indicate that [3H]azido-MBPE is a specific high affinity probe of ABS that will prove useful in the ultimate identification of this protein.
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PMID:A potent and selective photoaffinity probe for the anti-estrogen binding site of rat liver. 221 9

Active tumor promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or membrane-diffusible synthetic diacylglycerols such as 1,2-dioctanoyl-sn-glycerol (DiC8), which specifically activate protein kinase C (PKC), inhibited the agonist-mediated rise in cytosolic calcium [(Ca2+)i] in a mast cell line (PB-3c) and human platelets. TPA inhibition of agonist-mediated calcium transient in platelets was readily reversed by the PKC inhibitor staurosporine. In contrast to DiCs, only active tumor promoters induced a time- and dose-dependent translocation of cytosolic PKC to membranes as determined both enzymatically or by immunoblotting. However, the concentration of TPA required to induce a half-maximal subcellular redistribution of immunodetectable PKC activity was an order of magnitude greater than the half-maximal dose required to inhibit the intracellular rise in (Ca2+)i. Thus, activation of PKC seems not to be exclusively coupled to its translocation to membranes, suggesting that translocation of PKC is mainly involved in the down-regulation of PKC. Down-regulation of immunoprecipitable PKC was studied in various human breast cancer cell lines that display differential growth inhibitory responses toward the tumor promoter. TPA induced translocation of [35S]methionine-prelabeled cytosolic 80 kDa PKC to membranes followed by complete degradation of the enzyme (t1/2 = 2 h) without affecting PKC synthesis. During prolonged TPA exposure, 20-80% of total 80 kDa PKC of control cells was still synthetized as a membrane-bound 74/80 kDa PKC doublet. Although both proteins lacked PKC activity and phorbol ester binding, they revealed structural similarity with the active 80 kDa PKC form of untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of protein kinase C (PKC) in short- and long-term cellular responses: inhibition of agonist-mediated calcium transients and down-regulation of PKC. 246 82

Sodium butyrate and dimethylsulfoxide (DMSO), two known chemical inducers of cell differentiation, were examined on MCF-7 breast cancer cells. Both agents reduce the proliferative capacity of MCF-7 cells, as reflected by inhibition of colony formation in semisolid agar. Sodium butyrate is shown to enhance markedly the activity of two plasma membrane-bound enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase. DMSO does not enhance the activity of these enzymes, but rather induces a small decrease in gamma-glutamyl transpeptidase activity. The present results show that although both agents inhibit cell proliferation, they have a distinct effect on phenotypic expression.
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PMID:Differential effects of sodium butyrate and dimethylsulfoxide on gamma-glutamyl transpeptidase and alkaline phosphatase activities in MCF-7 breast cancer cells. 289 May 41

Active, structurally unrelated tumor promoters (12-0-tetradecanoyl-phorbol-13-acetate (TPA), teleocidin and aplysiatoxin) inhibit growth of mammary carcinoma cells (MCF7- greater than BT-20 greater than MDA-MB-231 greater than = ZR-75-1 greater than HBL-100). This efficiency in inhibiting cell growth correlates with the tumor-promoting activity of a series of phorbol ester derivatives. The phospholipid/calcium-dependent protein kinase (PKC), a target for phorbol ester action, was measured by polyacrylamide gel electrophoresis. The levels of PKC were higher (p less than 0.001) in estrogen-receptor-negative than in estrogen-receptor-positive cells. Treatment of cells with active tumor promoters results in time- and dose-dependent translocation of cytosolic PKC to membrane fractions. Less potent phorbol esters induce only partial translocation of PKC (i.e., decrease of cytosolic without increase in membrane-bound PKC), whereas inactive esters have no effect. No correlation was found between PKC concentration or the amount of PKC translocated to membranes and the sensitivity of the respective cells to TPA. It is concluded that tumor-promoter-mediated growth inhibition of breast cancer cell lines is due to mechanism(s) occurring after the translocation of PKC.
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PMID:Effects of tumor promoters on growth and on cellular redistribution of phospholipid/Ca2+-dependent protein kinase in human breast cancer cells. 308 90

The phorbol 12-myristate 13-acetate (PMA)-dependent down-regulation of immunoprecipitable protein kinase C was studied in human breast cancer cell lines that display different growth inhibitions toward the tumor promoter. PMA induces translocation of [35S]methionine-prelabeled cytosolic protein kinase C to membranes, followed by complete degradation of the enzyme (t1/2, 2 hr). PMA does not affect the protein kinase C synthesis; 20-80% of total protein kinase C of control cells was still immunoprecipitable as membrane-bound 74- and 80-kDa protein kinase C-related polypeptides if cells were allowed to incorporate [35S]methionine during PMA exposure for greater than 6 hr. These two proteins lack protein kinase activity and phorbol ester binding but reveal V8 peptide patterns identical to the active forms of protein kinase C (77/80 kDa) of PMA-untreated cells. The amounts of the immunoprecipitable membrane-bound 80-kDa protein kinase C-related polypeptide synthesized during the prolonged PMA treatment appear to inversely correlate with the extent of PMA-mediated growth inhibition of the respective human breast cancer cell line. These data suggest that after homologous down-regulation, functional protein kinase C (77/80 kDa) is replaced by a population of membrane-associated but enzymatically inactive protein kinase C-related polypeptides (74/80 kDa).
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PMID:Continuous synthesis of two protein-kinase-C-related proteins after down-regulation by phorbol esters. 335 68

The activity of the two membrane-bound sulfatases, estrone and dehydroepiandrosterone sulfatases, are reported in human breast carcinoma tissues. In 21 tested tumors (12 from post-menopausal women and 9 from nonmenopausal women), the two sulfatases were consistently present. The apparent Km values for estrone and dehydroepiandrosterone sulfatases were, respectively, 6.8 and 14.9 microM. In terms of maximal velocity, the sulfatase activities are not correlated to the estrogen or progesterone receptor status of the tumors or to the hormonal status of the donors. It may be concluded that these two activities are not hormone dependent. Estrone sulfate, the substrate of estrone sulfatase, has been measured in plasma of postmenopausal women. The mean levels (nmol/liter) of plasma estrone sulfate were compared in post-menopausal women with (n = 51) or without (n = 39) breast cancer. For the first age group (48 to 55 years old), no statistically significant difference in these levels was observed [1.91 +/- 1.06 versus 1.50 +/- 1.04 (mean +/- t0.95 (Formula: see text) S.E.)]. For the two other age groups (56 to 65 and 66 to 80 years of age), the differences were statistically significant [1.46 +/- 0.43 versus 0.77 +/- 0.21 (p less than 0.02) and 1.77 +/- 0.53 versus 0.81 +/- 0.22 (p less than 0.01)]. The usefulness of plasma estrone 3-sulfate levels as an indicator of the real estrogen status of postmenopausal women is discussed.
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PMID:Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. 658 63

A review of the current literature on immunohistologic and histochemical methods for the detection of steroid hormone binding sites in breast cancer, reveals that many, but not all of the criteria for establishing hormone-receptor binding interactions have been met. These include tissue specificity, binding between labeled ligands and soluble receptor in vitro, correlations between histochemical and biochemical assays, as well as between histologic procedures and tumor hormone responsiveness. However, histochemical binding phenomena do not appear to follow classical receptor dogma in regard to the concentration of ligand required, or specificity of binding as determined by competitive binding assays. It is concluded that these histologic techniques may be detecting classical receptor that may be reacting differently than would be expected from biochemical analyses, Types II and III binding sites, and/or organelle and membrane-bound receptors. Certainly no current method should presently be promoted as a laboratory method for the detection of classical receptor. New immunocytologic procedures employing specific, antireceptor sera currently under development, may obviate many of the criticisms leveled against earlier methods.
Breast Cancer Res Treat 1981
PMID:Immunohistologic and histochemical methods for detection of steroid binding in breast cancer: a reappraisal. 675 10

UDP-galactose:N-acetylglucosamine galactosyltransferase (GT) is a membrane-bound enzyme active in the biosynthesis of the carbohydrate moiety of glycoproteins and glycolipids. A soluble form of GT, present in human serum, has recently been found to be elevated in the presence of various neoplasms. In this study, GT levels were measured in randomized serum samples obtained from normal controls (group I, n = 49), patients with benign breast disease (group II, n = 46), disease controls (group III, n = 50), patients with primary breast carcinoma (group IV, n = 53), and untreated metastatic breast cancer (group V, n = 23). Although substantial serum GT elevations were observed in individual control patients with active inflammatory or metabolic diseases, the mean GT levels were significantly higher in the groups with breast carcinoma (P < 0.001, 0.001, 0.02; P < 0.001, 0.001, 0.001 for groups IV and V vs groups, 1, II, and III, respectively). Furthermore, when serum GT levels were correlated with the properative clinical stage of breast cancer, significant elevations were found in 14.3% (3/21) of stage I, 66.7% (8/12) of stage II, 78.6% (11/14) of stage III, and 96.5% (28/29) of stage IV patients. These data indicate that serum GT levels are elevated in the presence of breast carcinoma and that the enzyme elevations correlate positively with the clinical stage of disease. Serum GT may be potentially useful in the detection of recurrent breast carcinoma and as a marker of tumor response to therapy for advanced disease.
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PMID:Serum UDP-galactosyl transferase as a potential biomarker for breast carcinoma. 677 60


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