Transforming growth factor alpha- and c-myc-induced mammary carcinogenesis in transgenic mice

Teresa A. Rose-Hellekant, Eric P. Sandgren

Research output: Contribution to journalReview article

35 Scopus citations

Abstract

The growth factor transforming growth factor alpha (TGFα) and the nuclear transcription factor c-myc often are overexpressed by human breast cancer cells. To produce models of breast disease with these etiologies, mice were generated that carried TGF-α or c-myc-encoding transgenes. Transgene targeting employed the whey acidic protein (WAP) gene promoter, which is expressed in pregnant and lactating mammary epithelial cells. Non-virgin WAP-TGFα transgenic mice displayed accelerated mammary development during pregnancy, delayed post-parturient mammary involution, a progressive increase in the number of hyperplastic alveolar nodules (HANs), and development of mammary carcinoma with a mean latency of 9 months. Non-virgin WAP-c-myc transgenic mice displayed accelerated mammary gland development during pregnancy and development of mammary carcinomas with a latency of 8 months. Bitransgenic mice carrying both WAP-TGFα and WAP-c-myc displayed a dramatic acceleration of tumor development. These models identify the overexpression of TGFα or c-myc as etiological factors in the development of mammary neoplasia and demonstrate the increased severity of disease when both molecular alterations are present in the same cell.

Original languageEnglish (US)
Pages (from-to)1092-1096
Number of pages5
JournalOncogene
Volume19
Issue number8
DOIs
StatePublished - Feb 21 2000

Keywords

  • Mammary cancer
  • Transforming growth factor alpha
  • Transgenic mice
  • c-myc

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