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- Title
Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma.
- Authors
Wechselberger, Christian; Strizzi, Luigi; Kenney, Nicholas; Hirota, Morihisa; Sun, Youping; Ebert, Andreas; Orozco, Olivia; Bianco, Caterina; Khan, Nadia I.; Wallace-Jones, Brenda; Normanno, Nicola; Adkins, Heather; Sanicola, Michele; Salomon, David S.
- 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.Oncogene (2005) 24, 4094–4105. doi:10.1038/sj.onc.1208417 Published online 16 May 2005
- Subjects
HYPERPLASIA; MAMMARY glands; TUMOR growth; GENE expression; CANCER genetics; ONCOLOGY
- Publication
Oncogene, 2005, Vol 24, Issue 25, p4094
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208417