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)

The human milk fat globule (HMFG) membrane contains several glycoproteins that have been referred to as breast differentiation antigens and that are expressed in normal breast, breast tumors, breast tumor-derived cell lines, and are found in breast cancer patient serum. These antigens include a high molecular weight mucin and several smaller components including Mr 150,000; 70,000; and 46,000 glycoproteins. We have used 2 monoclonal antibodies (McR2 and Mc13) that bind the Mr 70,000 component of HMFG to immunoscreen a lambda gt11 expression library prepared from human lactating breast tissue. We report here the sequence of a complementary DNA clone (BA70-1) that codes for a peptide that binds both McR2 and Mc13 but not monoclonal antibodies to the breast mucin or other components of HMFG.A 1.8-kilobase RNA was detected in 9 of 9 breast tumor cell lines using 32P-labeled BA70-1 as probe. The BA70-1 RNA was highly expressed in 6 of 9 cells lines of breast and several other carcinomas lines compared with a lymphoblastoid cell line (Raji). The BA70-1 complementary DNA sequence has no extensive homology with previously reported sequences including the high-molecular weight mucin complementary DNA. Since the Mr 70,000 molecule appears to be associated with the breast mucin by disulfide bonds, its study could help elucidate the structure of this latter complex and how it is organized in the cell membrane, and prove useful in diagnosis and therapy of breast cancer.
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PMID:Cloning and sequencing of a complementary DNA encoding a Mr 70,000 human breast epithelial mucin-associated antigen. 239 62

We have previously defined a human mammary epithelial antigen using a murine monoclonal antibody (MAb), designated DF3, prepared against a membrane-enriched fraction of a human breast carcinoma. MAb DF3 detects a cell surface antigen with a molecular weight (mw) of approximately 300 Kd and a higher mw species also detectable in human milk. These findings and the demonstration that butyric acid (BA) increases DF3 antigen expression suggested that MAb DF3 reacts with a differentiation antigen detectable in human breast carcinoma cells. The results of the present study demonstrate that MAb DF3 reacts with two mucin-like high mw glycoproteins (330 and 450 Kd) present in MCF-7 breast carcinoma cells. The results also demonstrate that the intracellular content and secretion of DF3 antigen is increased by 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-beta-D-arabinofuranosylcytosine (ara-C). Other known inducers of differentiation including retinoic acid (RA), hexamethylene bisacetamide (HMBA), 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and certain polar solvents decrease DF3 antigen expression. Furthermore, the results demonstrate that DF3 antigen is secreted and that the extent coincides with changes in intracellular content. Finally, actinomycin D and cycloheximide inhibit the increases in DF3 antigen expression following TPA treatment thus suggesting that newly synthesized RNA and protein are required for induction of this antigen. Thus, the monitoring of DF3 antigen expression may provide a marker for studying maturation of human breast cancer cells.
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PMID:Effects of maturational agents on expression and secretion of two partially characterized high molecular weight milk-related glycoproteins in MCF-7 breast carcinoma cells. 241 36

The history of a patient presenting with metachronous bilateral breast cancer displaying histiocytoid features is reviewed. Although regional metastases were noted, this patient has not demonstrated an aggressive systemic disease pattern. In the past, histiocytoid breast cancer has been classified as either a lipid-rich carcinoma or as a variant of lobular carcinoma. However, histiocytoid carcinoma should be considered a distinct entity. Unlike the lipid-rich carcinomas, this tumor stained strongly for mucin. Immunoperoxidase staining indicated strong positively for CEA and negative staining for alpha-lactalbumin. There is suggestive evidence of a relationship between histiocytoid breast carcinoma and breast cancers of apocrine origin. Controversy remains and further evaluation is needed to elucidate the histiogenesis and biological potential of this neoplasm.
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PMID:Histiocytoid carcinoma: a variant of breast cancer. 242 90

Monoclonal antibody BR 15-6A directed to the Y carbohydrate determinant (Fuc alpha 1----2Gal beta 1----4GlcNAc(3----1Fuc) beta 1----3Gal beta 1----4Glc beta 1----1Cer) reacted with the cell surface and conditioned media of colorectal and breast carcinoma cell lines. Double determinant immunoassays using BR 15-6A as detector antibody showed that the Y determinant is part of a high molecular weight mucin that coexpressed other carbohydrate antigens based on a type 2 chain (X, H type 2). Type 1 chain carbohydrates such as sialylated Lewisa, Lewisa and Lewisb blood group antigens were predominantly expressed on a separate mucin molecule as determined by double-determinant immunoassays with other anticarbohydrate monoclonal antibodies. The X, Y, and H type 2-bearing mucin was present in conditioned media of the majority of colorectal carcinoma cell lines and in all three breast cancer cell lines tested. Thus, monoclonal antibodies against X, Y, and H type 2 determinants are potentially useful in the serodiagnosis of gastrointestinal and breast cancer.
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PMID:A mucin containing the X, Y, and H type 2 carbohydrate determinants is shed by carcinoma cells. 244 94

Monoclonal antibodies to mucin glycoproteins have previously been shown to detect elevated antigen levels in sera from breast cancer patients. To determine whether different mucin epitopes represent better targets for serum assays, we have produced and characterized 14 new monoclonal antibodies directed against the mucin glycoproteins detected by antibody W1. Many of the new antibodies differed from each other in their ability to bind to mucins from various sources. Cross-competition analyses of antibody binding indicated that while epitopes for some antibodies were distinct, most epitopes showed complex structural or steric relationships with those for other antibodies. Antibody M26 bound glycolipids from meconium and kidney, indicating that it recognized a carbohydrate epitope. Antibodies M15, M22, M23, and M27 bound to structurally or sterically related epitopes on deglycosylated milk-derived mucin, suggesting that they recognized core protein epitopes. Enzyme immunoassays were developed with the new antibodies and evaluated for their ability to discriminate between sera from breast cancer patients and from controls with benign breast disease. The best single test in terms of sensitivity and specificity used a combination of two antibodies, antibody M29 for antigen capture and antibody M38 for antigen detection. A second test using antibody M26 for antigen capture and antibody M38 for antigen detection detected elevated antigen levels in sera from some patients which were in the control range of the M29/M38 test. By combining results from these tests, significantly more cancer patients were detected than with the W1 and CA 15.3 tests.
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PMID:Monoclonal antibodies reactive with mucin glycoproteins found in sera from breast cancer patients. 245 Jun 46

Two monoclonal antibodies, TKH1 and TKH2, directed toward the sialosyl-Tn structure (NeuAc alpha 2----6GalNAc alpha 1----O-Ser or Thr), which display a remarkable immunohistological tumor specificity, were generated by immunization with ovine submaxillary mucin. The reactivity of these antibodies was monitored by solid phase enzyme-linked immunosorbent assay with different native and glycosidase-treated mucins and glycoproteins. Binding of the antibody to ovine submaxillary mucin glycoprotein was strongly inhibited by the O-linked disaccharide NeuAc alpha 2----6GalNAc alpha 1----O-serine, less strongly by NeuAc alpha 2----6GalNAc beta 1----O-propyl, and weakly by the monosaccharide GalNac. The reactivity was compared with previously established anti-Tn antibodies B72.3, NCC-Lu-35, and NCC-Lu-81. The antibody B72.3 was prepared previously after immunization with metastatic breast adenocarcinoma and its epitope was claimed to be GalNAc alpha 1----O-Ser (or - Thr) by Springer and associates [Springer, G.F., et al. In: T. Dao, et al. (eds.), Tumor Markers and Their Significance in the Management of Breast Cancer, pp. 47-70. New York: A.R. Liss, 1986]. The antibody was found to show very similar reactivity as that of TKH1/TKH2, and its reactivity to ovine submaxillary mucin was inhibited specifically by NeuAc alpha 2----6GalNAc alpha 1----O-serine, indicating that the antibody is clearly directed to sialosyl-Tn antigen. Immunohistological study of the distribution of this antigen in various normal human tissues and carcinomas by TKH1/TKH2 antibodies, as well as B72.3 and monoclonal antibodies NCC-Lu-35/81, which are directed to GalNAc alpha 1----O-Ser or Thr (Tn), was performed. The sialosyl-Tn antigen was not found in normal tissue except for a weak expression in Leydig cells of the testis, goblet cells of the colon, and parietal cells of the stomach. In contrast, the sialosyl-Tn antigen was strongly expressed in a large number of adenocarcinomas. As expected from the specificity studies, B72.3 shows the same reactivity as TKH1 and TKH2. Thus, both sialosyl-Tn (NeuAc alpha 2----6GalNAc alpha 1----O-Ser/Thr) and Tn (GalNAc alpha 1----O-Ser/Thr) are good tumor markers, and combined use of antibodies directed to these structures might be useful in the screening and classification of cancer.
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PMID:Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2----6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope. 245 Jun 49

During a follow-up program, breast cancer patients were monitored with serum analyses of mucin-like carcinoma-associated antigen (MCA), CA 15.3 and carcinoembryonic antigen (CEA). Minimum as well as maximum marker values of the individual patterns were selected for further evaluation. Marker levels of risk patients differed significantly from those of patients with metastases. In several risk patients, elevated marker levels (especially of MCA) preceded clinical diagnosis of metastases for several months. In cases with already diagnosed metastases, sensitivity of MCA was comparable to CA 15.3 or CEA. The type of metastases determined marker sensitivity, concentration and the difference between maximum and minimum values.
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PMID:Follow-up of metastatic breast cancer patients with a mucin-like carcinoma-associated antigen: comparison to CA 15.3 and carcinoembryonic antigen. 246 Dec 50

Three murine monoclonal antibodies (BC1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW greater than or equal to 230,000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co-expressed on the same molecules as 3E1.2-defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer-related mucin. However, the 3E1.2 epitope is distinct and non-cross-reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1.2 for antigen detection and gave reasonable sensitivity (approximately 85%) and specificity (approximately 95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.
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PMID:Monoclonal antibodies reactive with mucin expressed in breast cancer. 247 30

1. In previous studies we have isolated and characterized mucin-type glycopeptides from mouse and human melanoma cells. 2. These glycopeptides have clusters of oligosaccharides of the type (NeuNAc)0-2----[Gal----GalNAc] linked to serine and or threonine suggesting an apparent similarity to glycophorin. 3. We now report the interaction of polyclonal anti-glycophorin antibodies with various cultured cells. Antisera to highly purified glycophorin A were raised in rabbits. 4. Human melanoma cells (HM7), human breast cells (HBL-100) and two lines of human breast cancer cells (MCF-7 and MDA-MB-231) showed medium to very strong cell surface fluorescence pattern after staining with rabbit anti-glycophorin F(ab')2 and FITC-conjugated goat anti-rabbit F(ab')2. 5. Immunodiffusion, immunoelectrophoresis and affinity chromatography on anti-glycophorin IgG-Sepharose 4B of detergent extracts of metabolically labeled cultured cells gave further evidence for the presence of glycophorin-like components in these cells. 6. Glycoproteins of MCF-7 cells interacting with anti-glycophorin antibodies were affinity purified and partially characterized.
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PMID:Detection of glycophorin A-like glycoproteins on the surface of cultured human cells. 250 71

The nucleotide sequence of partial cDNA clones coding for the core protein of a human polymorphic epithelial mucin has recently been obtained, this mucin consists of a highly conserved 60 bp tandem repeat and the amino acids commonly found are PDTRPAPGSTAPPAHGVTSA. We synthesized three peptides, 1) P1.24 containing the 20 amino acids and four amino acids (PDTR) of the adjoining repeat; 2) P1.15 consisting of the first fifteen (PDTRPAPGSTAPPAH) and P1.09 the second nine amino acids (GVTSAPDTR) of peptide P1.24. The reactivities of the synthetic peptides with mAb known to react with breast cancer (BC1, BC2, BC3, HMFG-1, 3E1.2, and RCC-1) were studied. The synthetic peptide, P1.24, corresponding to the antigenic sequence predicted from the tandem repeat reacted with antibodies BC1, BC2, and BC3 (known to react with human milk mucin and mucin expressed in breast cancer) and the antibody HMFG-1 which was used to select the cDNA clones. In addition, the epitopes recognized by BC1, BC2, and BC3 appear to be in the same region of the molecule represented by their reactions with the nine amino acids in peptide P1.09 (GVTSAPDTR). By contrast, other antibodies such as 3E1.2 which reacts only weakly with components of human milk, and RCC-1 that detects a low Mr component (95 kDa) in breast cancer, had no specific reaction with the synthetic peptides, indicating that their epitopes are distinct from those of BC1, BC2, BC3, and HMFG-1. Inasmuch as the antibodies HMFG-1, BC1, BC2, and BC3 react with the fully processed milk mucin, it is likely that some of the peptide is exposed, even in the fully glycosylated molecule. Identification of the different epitopes could lead to the development of "second generation" mAb with enhanced specificity for breast carcinoma using the appropriate synthetic peptides as immunogens.
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PMID:Reactivity of anti-human milk fat globule antibodies with synthetic peptides. 271 33


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