Monoclonal antibodies reactive with mucin expressed in breast cancer

Xing, Pei‐Xiang; Tjandra, Joe J.; Stacker, Steven A.; Teh, Jin‐Ghee; Thompson, Christopher H.; McLaughlin, Paul; McKenzie, Ian F. C.

doi:10.1038/icb.1989.29

Cited by 110 publications

(75 citation statements)

References 28 publications

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“…For MUC1 staining, slides were deparaffinized in xylene, rehydrated, blocked in normal goat serum, and incubated with primary antibody anti-MUC1 BC2, a mouse monoclonal antibody that recognizes the epitope APDTR in the tandem repeat in MUC1; BC2 was a kind gift from Dr M McGuckin (University of Melbourne, Australia). Anti-MUC1 BC2 was diluted 1 : 20 000 in PBS with 1.5% normal goat serum (Xing et al, 1989). Sections were incubated with anti-MUC1 antibody overnight at 41C, followed by 2 Â 1 min PBS washes, 1 h incubation in HRP-conjugated anti-mouse (Pierce) diluted 1 : 500 in PBS with 1.5% normal goat serum, followed by 2 Â 1 min PBS washes.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Downregulation of Muc1 in MMTV-c-Neu tumors

Adriance

Gendler

2004

Oncogene

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MUC1 is a tumor antigen, overexpressed in approximately 90% of human breast cancers. In normal glandular epithelia, MUC1 is expressed at the apical surface; however, in carcinomas an aberrantly glycosylated form of MUC1 is upregulated and expressed around the entire surface of the cell. Previously, we have shown that a lack of Muc1 significantly delays tumor progression and/or onset in MMTV-PyV-mT and MMTV-Wnt-1 transgenic mice. Here we show that, unlike the models mentioned above, a loss of Muc1 in MMTV-c-Neu mice (MMTV-cNeu/Muc1 À/À ) altered neither mammary tumor onset nor progression. Moreover, characterization of MMTV-cNeu/Muc1 þ / þ tumors revealed that Muc1 expression was repressed at the level of transcription. In contrast, normal mammary gland tissue adjacent to tumor tissue expressed Muc1 and pregnant mammary glands from c-Neu transgenic animals expressed high levels of Muc1. We found that transient transfection of activated ErbB2 into human embryonic kidney 293/MUC1 cells resulted in the repression of MUC1 expression. Further, transient transfection of activated ErbB2 resulted in the inhibition of Muc1 transcriptional activation in luciferase reporter assays. These data suggest that the activation of ErbB2, which only occurs in c-Neu tumors, selectively inhibits Muc1 expression.

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Section: Immunohistochemistrymentioning

confidence: 99%

Downregulation of Muc1 in MMTV-c-Neu tumors

Adriance

Gendler

2004

Oncogene

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“…Mabs BC2 (IgGI), BC3 (IgM), 401/21 (IgGI), and FMI (IgM) were used as control antibodies (Xing et al, 1989;Skerritt & Hill, 1990;Devine et al, 1990b). BC2 and BC3 react with the minimum epitope APDTR on the MUCI VNTR , 401/21 reacts with wheat protein gliadins (Skerritt & Hill, 1990), while the specificity of FM1 has not been determined.…”

Section: Elisamentioning

confidence: 99%

Monoclonal antibodies reacting with the MUC2 mucin core protein

Pl¹,

McGuckin²,

Birrell³

et al. 1993

Br J Cancer

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Summary This study sought to produce monoclonal antibodies (MAbs) which reacted with the MUC2 core protein. Two MAbs [3A2 (IgGl) and 4F1 (IgM)] were produced by immunising female BALB/c mice with gel-formed mucin from the LS174T colon cancer cell line followed by a KLH conjugate of a 29 amino acid synthetic peptide whose sequence was derived from the variable number of tandem repeats (VNTR) region of a MUC2 cDNA clone.The MAbs reacted with synthetic MUC2 VNTR peptides but not synthetic MUCI or MUC3 VNTR peptides, and showed specific reactivity in Western blotting with a high molecular weight protein produced by the LS174T colon carcinoma cell line. The use of shorter peptides indicated that the minimum peptide epitopes for these MAbs were different. Mab 3A2 reacted with amino acids 5-19 of the MUC2 VNTR by inhibition ELISA but not by direct ELISA, while 4FI reacted with this peptide in both assays. Furthermore, 4FI reacted in direct ELISA when a larger (29 amino acid) MUC2-derived peptide was coated onto the assay plate by incubating in carbonate buffer or by drying the peptide onto the assay plate, while 3A2 only reacted when this peptide was coated in carbonate buffer. The different specificity of the MAbs was also illustrated by the reactivity of 4F1 but not 3A2 with partially deglycosylated cystic fibrosis mucin.Immunohistochemical analysis with these MAbs revealed a strong reactivity with lung, gastric and colon tumours relative to normal tissue, with some breast and ovarian tumours also reacting. Both MAbs stained some normal goblet cells in the perinuclear region but not the mucin droplet or secreted mucin, indicating a reaction with immature (poorly glycosylated) mucin in the endoplasmic reticulum and/or golgi, but not with mature (fully glycosylated) mucin. In contrast, tumours showed strong diffuse cytoplasmic staining. 4F1 also showed weak apical cytoplasmic staining in some goblet cells and stained some tumours which showed no reactivity with 3A2.These antibodies should prove useful in the study of MUC2 structure and function, and in the diagnosis of some tumours.

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“…Murine MoAb used for therapy included 30-6 (IgG2b), which is reactive against a large number of colon carcinoma cell lines (18), I-l and JGT (IgGl), which are both anti-CEA (carcinoembryonic antigen) (19). Irrelevant murine MoAb used to evaluate the HAMA response included BCl (IgGi), BC2 (igGl), and BC3 (IgM) which were directed against mucin-like glycoproteins of breast (20); and polyclonal antibodies of monkey and sheep origin (produced in our laboratory). MoAb 3E1 2 was purified from ascitic fluid (21) and the antibodies RCC-1 and Ly-21 were purified on Protein A-Sepharose (Pharmacia inc., Piscataway, New Jersey, USA as described previously (22); antibodies 30-6,1-1 and JGT by Protein A-Suparose (Pharmacia Inc., Piscataway, NJ).…”

Section: Murine Monoclonal Antibodiesmentioning

confidence: 99%

Development of human anti‐murine antibody (HAMA) response in patients

Tjandra¹,

Ramadi²

1990

Immunology & Cell Biology

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SummaryHuman anti‐mouse antibody (HAMA) response was determined in the scrum of 67 patients who received subcutaneously administered radiolabelled murine monoclonal antibodies (MoAb) (50 μg‐3 mg) for immunolymphoseintigraphy and of 10 patients with advanced colorectal cancer who received murine MoAb‐N‐acetyl melphalan (MoAb‐N‐AcMEL) conjugates (amount of MoAb ranged from 120 mg/m2 body surface area to 1000 mg/m2 body surfaee area) as therapy. A pre‐existing low level of apparent human anti‐mouse antibody reactivity could be detected in the serum of normal subjects and patients prior to administration of murine MoAb. Subcutaneous administration of low doses of murine MoAb, as used in immunolymphoscintigraphy, was associated with a low incidence (4/67 or 6%) of elevated HAMA response; the use of F(ab′)2 fragments was associated with the development of elevated HAMA response in one of three patients. By contrast, therapy with hepatic artery infusion of murine MoAb‐N‐AcMEL conjugates in three repetitive daily doses (each infusion lasting 2 h) elicited elevated HAMA responses in 10/10 (100%) patients, usually 1–3 weeks after the start of therapy. The HAMA response of patients in the therapy group was higher than those in the immunolymphoscintigraphy study and the use of steroids did not prevent the development of the HAMA response. Further administration of MoAb‐N‐AcMEL conjugates to a patient, who had already developed HAMA, led to ‘serum sickness’‐type symptoms and a transient reduction in the HAMA titres. The elevated HAMA response was polyclonal, containing increased levels of both immunoglobulin M and G (IgM and IgG) and was directed against mouse‐specific determinants, the isotype (presumed to be the Fc portion), the F(ab′)2 and the ‘idiotype’ of mouse immunoglobuiins.

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Monoclonal antibodies reactive with mucin expressed in breast cancer

Cited by 110 publications

References 28 publications

Downregulation of Muc1 in MMTV-c-Neu tumors

Downregulation of Muc1 in MMTV-c-Neu tumors

Monoclonal antibodies reacting with the MUC2 mucin core protein

Development of human anti‐murine antibody (HAMA) response in patients

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