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CITED1 homozygous null mice display aberrant pubertal mammary ductal morphogenesis

Oncogene volume 25, pages 1532–1542 (2006)Cite this article

Abstract

Expression microarray analysis identified CITED1 among a group of genes specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1 localizes to the luminal epithelial cell population of the mammary ducts and the body cells of the terminal end buds. Generation of CITED1 gene knockout mice showed that homozygous null mutants exhibit retarded mammary ductal growth at puberty and, in addition, dilated ductal structures with a lack of spatial restriction of the subtending branches. Analysis of CITED1 homozygous null and heterozygous null mammary gland gene expression using microarrays suggested that the mammary-specific phenotype seen in the homozygous null females is due to a disturbance in the transcription of a number of key mediators of pubertal ductal morphogenesis. These include estrogen and TGFβ responsive genes, such as the EGFR/ErbB2 ligand, amphiregulin, whose transcription we suggest is directly or indirectly regulated by CITED1.

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Acknowledgements

We gratefully acknowledge the support of Bohdan Wasylyk. We thank Joseph Mooney of the Biomedical Facility and Alison Murphy of the Conway Institute Microarray Core Facility, UCD for their technical assistance.

This work was supported by grants from Science Foundation Ireland and HRB, Ireland [inclusive of the Research Programme Grant: Breast Cancer Metastasis: Biomarkers and Functional Mediators] and IRCSET, Ireland; the EU RTN on Mammary Development and by US NIH Grant (CA082230) (to TS).

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Authors and Affiliations

  1. UCD Conway Institute and School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland

    J Howlin, J McBryan, S Napoletano, T Lambe, E McArdle & F Martin

  2. Laboratory of Tumour Biology, Massachusetts General Hospital Cancer Centre, Charlestown, MA, USA

    T Shioda

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  1. J Howlin
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  2. J McBryan
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  4. T Lambe
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  5. E McArdle
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  6. T Shioda
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  7. F Martin
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Correspondence to F Martin.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Howlin, J., McBryan, J., Napoletano, S. et al. CITED1 homozygous null mice display aberrant pubertal mammary ductal morphogenesis. Oncogene 25, 1532–1542 (2006). https://doi.org/10.1038/sj.onc.1209183

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