Monoclonal antibodies to epithelial sialomucins recognize epitopes at different cellular sites in adenolymphomas of the parotid gland

Zotter, Stefan; Hageman, Ph.; Lossnitzer, A.; Tweel, J. Den Van; Hilkens, John; Mooi, Wolter J.; Hilgers, J.

doi:10.1002/ijc.2910410809

Cited by 49 publications

(44 citation statements)

References 24 publications

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“…It is interesting to note that MUC1 is highly expressed in invasive disease, while the overexpression of ErbB2 predominates earlier in tumor development. MUC1 is overexpressed in approximately 90% of human breast cancers, while ErbB2 overexpression occurs in 80% of DCIS and 25% of invasive cancers (Slamon et al, 1987;Zotter et al, 1988;Revillion et al, 1998;Witton et al, 2003). In human cancers, oncogenic activation of ErbB2 is generally thought to occur mostly due to the overexpression of ErbB2, and not activation.…”

Section: Discussionmentioning

confidence: 99%

“…MUC1 is found to be overexpressed in approximately 90% of human breast cancers, with a clinical significance of poor patient prognosis (Zotter et al, 1988;McGuckin et al, 1995;Croce et al, 2003). Further, increases in MUC1 expression at least as high as ten fold have been detected (Hilkens et al, 1984); however, the processes responsible for the stimulation of MUC1 expression during cancer are currently unclear.…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of Muc1 in MMTV-c-Neu tumors

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Downregulation of Muc1 in MMTV-c-Neu tumors

Adriance

Gendler

2004

Oncogene

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“…While MUC1 has been identified as aberrantly expressed in greater than 90% of human breast carcinomas (Zotter et al, 1988;Girling et al, 1989), the identification of a functional role for that overexpression has been elusive. Transgenic and knockout mice have provided insight into the role of MUC1 in tumor development, with the loss of Muc1 resulting in a reduction in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation

et al. 2004

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MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as b-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and b-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.

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“…High molecular weight glycoproteins, described as mucins or mucin-like glycoproteins, are frequently found associated with breast carcinoma and other epithelial cell adenocarcinomas (Zotter et al, 1988). Cancerassociated MUC1 is structurally different from normal MUC1 in that the former has shorter and less dense O-glycan chains, exposing novel regions of the protein core.…”

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confidence: 99%

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

et al. 2004

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Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using 213 Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of 213 Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in B90% of tested tumour samples and the three pancreatic cancer cell lines. 213 Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel 213 Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. 213 Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.

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Monoclonal antibodies to epithelial sialomucins recognize epitopes at different cellular sites in adenolymphomas of the parotid gland

Cited by 49 publications

References 24 publications

Downregulation of Muc1 in MMTV-c-Neu tumors

Downregulation of Muc1 in MMTV-c-Neu tumors

MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

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