The nuclear receptor interacting factor-3 transcriptional coregulator mediates rapid apoptosis in breast cancer cells through direct and bystander-mediated events

Sharmistha Das, Jerome C. Nwachukwu, Dangsheng Li, Anthony I. Vulin, Sonia Martinez-Caballero, Kathleen W. Kinnally, Herbert H. Samuels

Research output: Contribution to journalArticle

Abstract

We previously reported that amino acids 20 to 50 of nuclear receptor interacting factor-3 mediates rapid apoptosis in breast cancer cell lines but not in cells derived from other tissues. We refer to this short region as death domain-1 (DD1). Small interfering RNA studies indicated that DD1-mediated apoptosis is caspase-2 dependent. In this study, we examined DD1-mediated apoptosis in more detail and generated stable caspase-2 knockdown breast cancer cells. These cells are resistant to DD1-mediated apoptosis. Time-lapse movies suggested that DD1-mediated apoptosis also leads to a "bystander effect." We found that within 5 h of DD1 expression, breast cancer cells release a factor(s) into the medium that leads to apoptosis of naive breast cancer cells or DD1-resistant cells (e.g., HeLa). The DD1-expressing caspase-2 knockdown cells also release a factor(s) that kills other cells, indicating that this effect is not dependent on the apoptogenic process. The bystander effect seems dependent on the production of reactive oxygen species (ROS). These and other studies indicate that DD1 expression in breast cancer cells leads to at least two death signals: one involving the rapid production of ROS and/or other soluble factors that directly or indirectly leads to a bystander effect and a second caspase-2-dependent process that leads to apoptosis in cells in which DD1 is expressed.

Original languageEnglish (US)
Pages (from-to)1775-1782
Number of pages8
JournalCancer Research
Volume67
Issue number4
DOIs
StatePublished - Feb 15 2007

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Cytoplasmic and Nuclear Receptors
Apoptosis
Breast Neoplasms
Caspase 2
Bystander Effect
Reactive Oxygen Species
Death Domain
Motion Pictures
HeLa Cells
Small Interfering RNA
Cell Death
Amino Acids
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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The nuclear receptor interacting factor-3 transcriptional coregulator mediates rapid apoptosis in breast cancer cells through direct and bystander-mediated events. / Das, Sharmistha; Nwachukwu, Jerome C.; Li, Dangsheng; Vulin, Anthony I.; Martinez-Caballero, Sonia; Kinnally, Kathleen W.; Samuels, Herbert H.

In: Cancer Research, Vol. 67, No. 4, 15.02.2007, p. 1775-1782.

Research output: Contribution to journalArticle

Das, Sharmistha ; Nwachukwu, Jerome C. ; Li, Dangsheng ; Vulin, Anthony I. ; Martinez-Caballero, Sonia ; Kinnally, Kathleen W. ; Samuels, Herbert H. / The nuclear receptor interacting factor-3 transcriptional coregulator mediates rapid apoptosis in breast cancer cells through direct and bystander-mediated events. In: Cancer Research. 2007 ; Vol. 67, No. 4. pp. 1775-1782.
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