Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosis

Dorraya El-Ashry, David L. Miller, Samir Kharbanda, Marc E Lippman, Francis G. Kern

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Abstract

Overexpression of many growth factor receptors, as well as growth factors, has been shown to confer varying degrees of estrogen-independent growth on estrogen receptor (ER) positive breast cancer cells. The protooncogene Raf-1 is a key intermediate in the signal transduction pathway of many of these growth factor receptors, and when constitutively activated in fibroblasts is transforming. To examine the effects of Raf-1 kinase activity on the estrogen-dependent growth of human breast cancer cells, ER + MCF-7 breast cancer cells were stably transfected with an expression construct directing the expression of an amino-truncated protein having constitutive kinase activity. Expression of constitutively activated Raf in MCF-7 cells is incompatible with growth in the presence of estrogen; that is, cells down-regulate expression of the transfected Raf. Constitutive Raf activity does allow for growth of the cells in the absence of estrogen, suggesting that activation of growth factor signaling pathways through Raf may confer a selective advantage for growth of breast cancer cells under estrogen-deprived conditions. In addition, the high levels of Raf activity induce apoptosis in cells grown under either condition. This is a novel activity for Raf, and may occur because the levels of the constitutive Raf are extremely high in these cells.

Original languageEnglish
Pages (from-to)423-435
Number of pages13
JournalOncogene
Volume15
Issue number4
StatePublished - Sep 15 1997
Externally publishedYes

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Keywords

  • Apoptosis
  • Breast cancer
  • Estrogen-independence
  • Raf-1 kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

El-Ashry, D., Miller, D. L., Kharbanda, S., Lippman, M. E., & Kern, F. G. (1997). Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosis. Oncogene, 15(4), 423-435.