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Serial analysis of gene expression in normal p53 null mammary epithelium

Oncogene volume 21, pages 6366–6376 (2002)Cite this article

Abstract

Much evidence has accumulated implicating the p53 gene as of importance in breast carcinogenesis. However, much still remains to be uncovered on the specific downstream pathways influenced by this important activator/repressor of transcription. This study investigated the effects of a p53 null genotype on the transcriptome of ‘normal’ mouse mammary epithelium using a unique in vivo model of preneoplastic transformation. We used SAGE for the comparative analysis of p53 wild type (wt) and null mammary epithelium unexposed and exposed to hormonal stimulation. Analysis of the hormone exposed samples provided a comprehensive view of the dramatic changes in gene expression as consequence of the functional differentiation of the mammary epithelium in an in vivo system. We detected the dysregulation in p53null epithelium of <1% of the transcriptome. Changes in expression affected not only known p53 target genes, but also several unexpected genes such as Expi (Wdnm1), Cyp1b1, Gelsolin, Ramp2 and class I MHC genes. The dysregulation of specific genes and their potential use as preneoplastic markers was further validated using an independent model of premalignant mammary outgrowth lines. This is the first study to examine the transcriptome of very early stages of preneoplastic progression in an in vivo model that mimics human breast cancer.

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Acknowledgements

This work was supported by NIH Grant CA84243 and NIEHS Center Grant ES07784. We gratefully acknowledge Rebecca Deen for manuscript preparation and Joi Holcomb for preparation of artwork.

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Authors and Affiliations

  1. Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, 78957, Texas, TX, USA

    C Marcelo Aldaz, Yuhui Hu, Rachael Daniel & Sally Gaddis

  2. Baylor College of Medicine Department of Molecular and Cellular Biology, Houston, 77030, Texas, TX, USA

    Frances Kittrell & Daniel Medina

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  1. C Marcelo Aldaz
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  2. Yuhui Hu
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  3. Rachael Daniel
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  4. Sally Gaddis
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  5. Frances Kittrell
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  6. Daniel Medina
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Correspondence to C Marcelo Aldaz.

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Aldaz, C., Hu, Y., Daniel, R. et al. Serial analysis of gene expression in normal p53 null mammary epithelium. Oncogene 21, 6366–6376 (2002). https://doi.org/10.1038/sj.onc.1205816

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