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Initiating oncogenic event determines gene-expression patterns of human breast cancer models

  1. Author:
    Desai, K. V.
    Xiao, N.
    Wang, W.
    Gangi, L.
    Greene, J.
    Powell, J. I.
    Dickson, R.
    Furth, P.
    Hunter, K.
    Kucherlapati, R.
    Simon, R.
    Liu, E. T.
    Green, J. E.

  2. Author Address

    NCI, Lab Cell Regulat & Carcinogenesis, NIH, 41 Lib Dr,Room C619, Bethesda, MD 20892 USA NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA NCI, Ctr Adv Technol, Bethesda, MD 20892 USA NCI, Frederick Canc Res & Dev Ctr, Microarray Core Facil, Frederick, MD 21702 USA NIH, Ctr Informat Technol, Bethesda, MD 20892 USA Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA NIH, Lab Populat Genet, Bethesda, MD 20892 USA Harvard Partners Ctr Genet & Genomics, Boston, MA 02115 USA Green JE NCI, Lab Cell Regulat & Carcinogenesis, NIH, 41 Lib Dr,Room C619, Bethesda, MD 20892 USA
    1. Year: 2002
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 99
    2. 10
    3. Pages: 6967-6972
  4. Type of Article: Article
  1. 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.

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