Initiating oncogenic event determines gene-expression patterns of human breast cancer models
- Kartiki V. Desai*,
- Nianqing Xiao†,
- Weili Wang*,
- Lisa Gangi‡,
- John Greene§,
- John I. Powell§,
- Robert Dickson¶,
- Priscilla Furth¶,
- Kent Hunter‖,
- Raju Kucherlapati**,
- Richard Simon†,
- Edison T. Liu‡‡,††, and
- Jeffrey E. Green*,‡‡,§§
- *Laboratory of Cell Regulation and Carcinogenesis, †Molecular Statistics and Bioinformatics, ‡‡Advanced Technology Center, National Cancer Institute, Bethesda, MD 20892; ‡Microarray Core Facility, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD 21702; §Center for Information Technology, National Institutes of Health, Bethesda, MD 20892; ¶Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007; ‖Laboratory of Population Genetics, National Institutes of Health, Bethesda, MD 20892; and **Harvard Partners Center for Genetics and Genomics, Boston, MA 02115
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Communicated by Richard D. Klausner, National Academy of Sciences, Washington, DC (received for review November 5, 2001)
Abstract
Molecular expression profiling of tumors initiated by transgenic overexpression of c-myc, c-neu, c-ha-ras, polyoma middle T antigen (PyMT) or simian virus 40 T/t antigen (T-ag) targeted to the mouse mammary gland have identified both common and oncogene-specific events associated with tumor formation and progression. The tumors shared great similarities in their gene-expression profiles as compared with the normal mammary gland with an induction of cell-cycle regulators, metabolic regulators, zinc finger proteins, and protein tyrosine phosphatases, along with the suppression of some protein tyrosine kinases. Selection and hierarchical clustering of the most variant genes, however, resulted in separating the mouse models into three groups with distinct oncogene-specific patterns of gene expression. Such an identification of targets specified by particular oncogenes may facilitate development of lesion-specific therapeutics and preclinical testing. Moreover, similarities in gene expression between human breast cancers and the mouse models have been identified, thus providing an important component for the validation of transgenic mammary cancer models.
Footnotes
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↵ †† Present address: Genome Institute of Singapore, Singapore 117604.
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↵ §§ To whom reprint requests should be addressed at: Laboratory of Cell Regulation and Carcinogenesis, 41 Library Drive, Room C619, National Institutes of Health, Bethesda, MD 20892. E-mail: jegreen{at}nih.gov.
- Abbreviations:
- MMTV,
- mouse mammary tumor virus;
- EST,
- expressed sequence tag;
- PCNA,
- proliferating cell nuclear antigen
- Copyright © 2002, The National Academy of Sciences
