Downregulation of Muc1 in MMTV-c-Neu tumors

Melissa C. Adriance, Sandra J Gendler

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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-c-Neu/Muc1-/-) altered neither mammary tumor onset nor progression. Moreover, characterization of MMTV-c-Neu/Muc1+/+ 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.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalOncogene
Volume23
Issue number3
DOIs
StatePublished - Jan 22 2004

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Down-Regulation
Human Mammary Glands
Transfection
Neoplasms
Breast Neoplasms
Genetically Modified Animals
Neoplasm Antigens
Luciferases
Transgenic Mice
Transcriptional Activation
Epithelium
Carcinoma
Kidney

Keywords

  • erbB receptors
  • ErbB2
  • MUC1
  • Transmembrane mucin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Downregulation of Muc1 in MMTV-c-Neu tumors. / Adriance, Melissa C.; Gendler, Sandra J.

In: Oncogene, Vol. 23, No. 3, 22.01.2004, p. 697-705.

Research output: Contribution to journalArticle

Adriance, Melissa C. ; Gendler, Sandra J. / Downregulation of Muc1 in MMTV-c-Neu tumors. In: Oncogene. 2004 ; Vol. 23, No. 3. pp. 697-705.
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