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)

A panel of three monoclonal antibodies (MoAbs) was tested on 29 benign and 53 malignant effusions with the aim of investigating its usefulness for the discrimination between benign and malignant lesions. The panel consisted of MoAbs directed against epithelial membrane antigen (EMA); MCA-b-12, reacting with a 350 kD glycoprotein with mucin-like characteristics present on human breast cancer cells and various other normal and neoplastic tissues, and Ber-EP4, directed against a 34 and 39 kD glycopeptide on human epithelial cells but not on mesothelium. Fifty-two (98%) of the malignant effusions reacted with EMA, 49 (92%) with MCA-b-12 and 44 (83%) with Ber-EP4. Fourteen per cent of benign effusions reacted with EMA, 17% with MCA-b-12 and 7% with Ber-EP4. All seven effusions obtained from patients with a malignant mesothelioma reacted with EMA, six of the seven cases staining intensively. None of the seven stained with Ber-EP4. MCA-b-12 did not react with the cells in one case of malignant mesothelioma. The results suggest that the combination of EMA and Ber-EP4 may be used to discriminate between benign and malignant cells and possibly also between adenocarcinoma and malignant mesothelioma. MCA-b-12 followed in general the reaction pattern of EMA, although often with a less intense staining reaction, making this antibody unsuitable for inclusion in the panel.
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PMID:Identification of malignant cells in serous effusions using a panel of monoclonal antibodies Ber-EP4, MCA-b-12 and EMA. 128 55

We have purified and characterized a novel 30-kDa glycoprotein (gp30) with TGF alpha-like properties secreted from the estrogen receptor negative breast cancer cell line MDA-MB-231. This factor was immunoprecipitated by an anti-TGF alpha polyclonal antibody and also had TGF alpha-like biological activity, as assayed by EGF radioreceptor assay and anchorage-independent assays. In addition, the novel growth factor stimulated phosphorylation of the EGF receptor and erbB-2 receptor. However, the novel growth factor, unlike EGF and TGF alpha, bound to heparin-Sepharose. Purification of gp30 was obtained to apparent homogeneity by heparin affinity chromatography and subsequent reversed-phase chromatography. Tunicamycin treatment in vivo or N-glycanase deglycosylation in vitro revealed a putative precursor of approximately 22 kDa molecular mass in contrast to the "normal" 16-kDa precursor species for TGF alpha. In vitro translation of total mRNA from MDA-MB-231 cells confirmed the size of the putative precursor. Biochemical characterization of gp30 was begun by V8 protease digestion of the deglycosylated polypeptide and the translated products. Peptide mapping of V8-digested, immunoprecipitated material suggests that the amino acid sequence of this unique protein is distinct from mature TGF alpha and not the result of a posttranslational modification of the precursor. We conclude that this TGF alpha-like (gp30) polypeptide is a novel growth factor with agonistic activity for both EGF and erbB-2 receptors.
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PMID:Purification and characterization of a novel growth factor from human breast cancer cells. 132 10

The neu/HER-2 proto-oncogene (also called erbB-2) encodes a transmembrane glycoprotein related to the epidermal growth factor receptor. We have purified to homogeneity a 44 kd glycoprotein from the medium of ras-transformed cells that stimulates phosphorylation of the Neu protein and retains activity after elution from the polyacrylamide gel. The protein is active at picomolar concentrations and displays a novel N-terminal sequence. Cross-linking experiments with radiolabeled p44 result in specific labeling of Neu, indicating that p44 is a ligand for Neu or a related receptor. The purified protein induces phenotypic differentiation of cultured human breast cancer cells, including altered morphology and synthesis of milk components. This is accompanied by an increase in nuclear area, inhibition of cell growth (probably by cell cycle arrest at the late S or the G2/M phases), and induction of DNA polyploidy. We propose the name Neu differentiation factor (NDF) for p44.
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PMID:Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. 134 15

The neu/erbB-2 protooncogene encodes a transmembrane tyrosine kinase homologous to receptors for polypeptide growth factors. The oncogenic potential of the presumed receptor is released through multiple genetic mechanisms including a point mutation, truncation of non-catalytic sequences and overexpression. The latter mechanism appears to be relevant to human cancers as elevated expression of the neu/erbB-2 gene is frequently observed in solid tumors of various adenocarcinomas. It is therefore conceivable that strategies aimed at the biochemical mechanism of action of the neu/erbB-2 tyrosine kinase may contribute to the treatment of certain human cancers. To this aim we undertook a multiple research approach consisting of the following directions: (i) The neu/erbB-2 ligand--a systematic screening of potential biological sources of the hypothetical hormone molecule, that presumably binds to the neu/erbB-2 protein, resulted in detection of a candidate activity in the medium of certain cultured transformed cells. Partial purification indicated that the factor is a 30-35 kDa glycoprotein. Further studies revealed several biochemical characteristics of the factor that may be helpful for complete purification and structural analysis of this novel hormone. (ii) Signal transduction by neu/erbB-2--using a chimeric receptor approach and various mutants we found that all the oncogenic forms of the neu/erbB-2 are constitutively coupled, both physically and functionally, to a multi-protein complex of signaling molecules. The latter includes the phosphatidylinositol-specific phospholipase C gamma and a phosphatidylinositol kinase. Thus, the metabolism of inositol lipids is probably a major biochemical pathway utilized by the neu/erbB-2 tyrosine kinase. (iii) Tumor inhibitory antibodies--we generated a panel of monoclonal antibodies to the presumed receptor. Surprisingly, some antibodies almost completely inhibited the growth of tumor cells in athymic mice, whereas one antibody significantly accelerated the rate of tumor growth in animals. Interestingly, the inhibitory antibodies conferred a mature phenotype to cultured breast cancer cells, implicating terminal differentiation in tumor retardation.
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PMID:Signal transduction by the neu/erbB-2 receptor: a potential target for anti-tumor therapy. 135 18

Thrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 ng/ml with a mean of 365 ng/ml. In contrast, elevated levels of TSP greater than the mean value of 400 ng/ml for controls ranging between 590-3,650 ng/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.
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PMID:Thrombospondin levels in patients with malignancy. 150

Recent elucidation of the amino acid sequence of the progesterone-binding protein GCDFP-24, the major protein found in human breast gross cystic disease fluid, reveals that this glycoprotein corresponds to apolipoprotein-D (apo-D), a member of the alpha 2-microglobulin superfamily which binds small hydrophobic ligands. The present study describes the multiple hormonal control of apo-D mRNA levels, intracellular protein content, as well as secretion compared to cell proliferation in human ZR-75-1 breast cancer cells. In these cells, exposure to the synthetic glucocorticoid dexamethasone (DEX) markedly decreases basal as well as 17 beta-estradiol (E2)-induced cell proliferation while causing a maximal 10-fold stimulation of apo-D secretion in the presence or absence of E2. Incubation with 500 nM DEX or 10 nM dihydrotestosterone (DHT), alone and in combination, markedly increased apo-D mRNA/actin mRNA ratios by 16-, 22-, and 28-fold, respectively. Exposure to 1 nM E2 decreased the apo-D mRNA/actin mRNA ratio by 65%. In E2-treated cells, simultaneous exposure to DHT, DEX, and DHT plus DEX markedly increased the apo-D mRNA/actin mRNA ratios by 50-, 35-, and 105-fold, respectively. The stimulatory effect of DEX on intracellular apo-D content and secretion was also additive to that of the androgen DHT in the presence or absence of E2. The present study provides the first data describing the hormonal regulation of apo-D mRNA levels and intracellular protein content and demonstrates the effect of glucocorticoids alone as well as their interaction with androgens and estrogens on these parameters as well as on apo-D secretion. As shown in the present data, the effects of steroids on apo-D gene expression, intracellular apo-D protein content, and secretion are opposite their respective specific effects on cell proliferation in human ZR-75-1 breast cancer cells.
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PMID:Additive stimulatory action of glucocorticoids and androgens on basal and estrogen-repressed apolipoprotein-D messenger ribonucleic acid levels and secretion in human breast cancer cells. 153 79

The synthesis of a 66 kDa protein immunoreactive with antibodies to human alpha 1-antichymotrypsin (alpha 1-ACT) is induced by estradiol (E2) in the human breast cancer cell line MCF-7. We have purified this alpha 1-ACT-like 66 kDa protein from medium conditioned by MCF-7 cells, performed a comparative physico-chemical characterization with serum alpha 1-ACT, and analysed its presumed positive regulatory effect on growth of MCF-7 cells. The 66 kDa protein is a functional antiproteinase which is antigenically identical to serum alpha 1-ACT. The 66 kDa protein does however deviate from serum alpha 1-ACT with respect to mol. wt. and pattern of microheterogeneity, the molecular mechanism for this is probably an incomplete glycoprotein processing in the MCF-7 cells. The results of our growth experiments suggest that the 66 kDa protein is a minor positive growth regulatory factor, which may contribute to breast carcinoma cell proliferation in a cooperative manner.
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PMID:Purification and characterization of an alpha 1-antichymotrypsin-like 66 kDa protein from the human breast cancer cell line, MCF-7. 159 33

Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF-7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system.
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PMID:Response of human breast cancer cells to heat shock and chemotherapeutic drugs. 161 38

Episialin, a mucus glycoprotein, is a well-known tumor-associated antigen used in a variety of tests to detect the presence of adenocarcinoma. With the introduction of the microparticle-captured enzyme immunoassay (MEIA), a new technique was introduced. We compared this assay with our standard method to detect adenocarcinomas, the measurement of carcinoembryonic antigen (CEA). In breast cancer, the breast cancer mucin (BCM) assay was more often positive in metastatic disease but was not better than CEA in stages I-III. In lung carcinomas, BCM and CEA gave similar results while in colorectal carcinoma, CEA was superior. BCM gave similar results to CA 15.3 in a group of breast cancer patients.
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PMID:Breast cancer mucin: an automated assay to detect mucus glycoproteins. 162 80

Breast cancer is the leading cause of cancer deaths among females, and it is estimated that each year, one in ten American women will be newly diagnosed as having the disease. It is therefore not surprising, that a great deal of effort has been made to better understand the biology of breast cancer, and that investigators keep up the search for new tools to better characterize, diagnose and treat these tumours. In this regard, the introduction of the hybridoma technique in 1975 by Kohler and Milstein has lead to an extensive work in the characterization of monoclonal and polyclonal antibodies against breast cancers. A large number of antibodies has been raised to different epitopes present in normal and neoplastic breast tissue; but unfortunately we have yet to find a highly sensitive and specific monoclonal antibody for breast cancer that can successfully be used for scintigraphic detection of nodal metastases and for radioimmunotherapy treatment of this disease. As possible radioimmunodiagnostics, antibodies are known which react with the following antigens: (1) cytoskeletal proteins (2) breast cell products (3) steroid receptors (4) putative tumor-associated antigens (5) oncogene products (6) pregnancy-related products (7) basement membrane antigens (8) degradative enzymes (9) cell receptors for extracellular matrix molecules (10) multidrug resistance gene product (p-glycoprotein) (11) proliferative markers.
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PMID:Monoclonal antibodies for radioimmunoscintigraphy of breast cancer. 165 Jul 67


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