Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma

Christian Wechselberger, Luigi Strizzi, Nicholas Kenney, Morihisa Hirota, Youping Sun, Andreas Ebert, Olivia Orozco, Caterina Bianco, Nadia I. Khan, Brenda Wallace-Jones, Nicola Normanno, Heather Adkins, Michele Sanicola, David S. Salomon*

*Corresponding author for this work

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Human Cripto-1 (CR-1) is overexpressed in approximately 80% of human breast, colon and lung carcinomas. Mouse Cr-1 upregulation is also observed in a number of transgenic (Tg) mouse mammary tumors. To determine whether CR-1 can alter mammary gland development and/or may contribute to tumorigenesis in vivo, we have generated Tg mouse lines that express human CR-1 under the transcriptional control of the mouse mammary tumor virus (MMTV). Stable Tg MMTV/CR-1 FVB/N lines expressing different levels of CR-1 were analysed. Virgin female MMTV/CR-1 Tg mice exhibited enhanced ductal branching, dilated ducts, intraductal hyperplasia, hyperplastic alveolar nodules and condensation of the mammary stroma. Virgin aged MMTV/CR-1 Tg mice also possessed persistent end buds. In aged multiparous MMTV/CR-1 mice, the hyperplastic phenotype was most pronounced with multifocal hyperplasias. In the highest CR-1-expressing subline, G4, 38% (12/31) of the multiparous animals aged 12-20 months developed hyperplasias and approximately 33% (11/31) developed papillary adenocarcinomas. The long latency period suggests that additional genetic alterations are required to facilitate mammary tumor formation in conjunction with CR-1. This is the first in vivo study that shows hyperplasia and tumor growth in CR-1-overexpressing animals.

Original languageEnglish (US)
Pages (from-to)4094-4105
Number of pages12
JournalOncogene
Volume24
Issue number25
DOIs
StatePublished - Jun 9 2005

Keywords

  • Cripto-1
  • MMTV-LTR
  • Mammary development
  • Mammary tumorigenesis
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Wechselberger, C., Strizzi, L., Kenney, N., Hirota, M., Sun, Y., Ebert, A., Orozco, O., Bianco, C., Khan, N. I., Wallace-Jones, B., Normanno, N., Adkins, H., Sanicola, M., & Salomon, D. S. (2005). Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma. Oncogene, 24(25), 4094-4105. https://doi.org/10.1038/sj.onc.1208417