Hpr6.6 Protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells

Randal Hand, Rolf J. Craven

Research output: Contribution to journalArticle

Abstract

Reactive oxygen species (ROS) cause cell death and are associated with a variety of maladies, from trauma and infection to organ degeneration and cancer. Cells mount a complex response to oxidative damage that includes signaling from transmembrane receptors and intracellular kinases. We have analyzed the response to oxidative damage in human breast cancer cells expressing the Hpr6.6 (human membrane progesterone receptor) protein. Although Hpr6.6 is related to a putative progesterone-binding protein, Hpr6.6 is widely expressed in epithelial tissues and shares close homology with a budding yeast damage response protein called Dap1p (damage response protein related to membrane progesterone receptor). We report here that the Hpr6.6 protein regulates the response to oxidative damage in breast cancer cells. Expression of Hpr6.6 in MCF-7 cells sensitized the cells to death following long-term/low dose or short-term/high dose treatment with hydrogen peroxide. Cell death did not occur through a typical apoptotic mechanism and corresponded with hyperphosphorylation of the Akt and IκB proteins. However, inhibition of Akt activation and IκB degradation had no effect on Hpr6.6-mediated cell death, suggesting that Hpr6.6 regulates cell death through a novel oxidative damage response pathway. Our work indicates a key regulatory function for Hpr6.6 in epithelial tissues exposed to oxidative damage.

Original languageEnglish (US)
Pages (from-to)534-547
Number of pages14
JournalJournal of Cellular Biochemistry
Volume90
Issue number3
DOIs
StatePublished - Oct 15 2003
Externally publishedYes

Fingerprint

Cell death
Cell Death
Cells
Breast Neoplasms
Progesterone Receptors
Proteins
Progesterone-Binding Globulin
Epithelium
Tissue
Membranes
Saccharomycetales
MCF-7 Cells
Yeast
Hydrogen Peroxide
Cause of Death
Reactive Oxygen Species
Phosphotransferases
Chemical activation
Degradation
Wounds and Injuries

Keywords

  • Breast cancer
  • Cell death
  • Oxidative damage
  • Proliferation
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hpr6.6 Protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells. / Hand, Randal; Craven, Rolf J.

In: Journal of Cellular Biochemistry, Vol. 90, No. 3, 15.10.2003, p. 534-547.

Research output: Contribution to journalArticle

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