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Molecular and Cellular Biology, May 2004, p. 3838-3848, Vol. 24, No. 9
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.9.3838-3848.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The NRIF3 Family of Transcriptional Coregulators Induces Rapid and Profound Apoptosis in Breast Cancer Cells

Dangsheng Li,* Sharmistha Das, Tatsuya Yamada, and Herbert H. Samuels*

Department of Pharmacology, New York University School of Medicine, New York, New York 10016

Received 7 November 2003/ Returned for modification 16 December 2003/ Accepted 4 February 2004

Many anticancer drugs kill cancer cells by inducing apoptosis. Despite the progress in understanding apoptosis, how to harness the cellular death machinery to selectively deliver tumor-specific cytotoxicity (while minimizing damage to other cells) remains an important challenge. We report here that expression of the NRIF3 family of transcriptional coregulators in a variety of breast cancer cell lines induces rapid and profound apoptosis (nearly 100% cell death within 24 h). A novel death domain (DD1) was mapped to a short 30-amino-acid region common to all members of the NRIF3 family. Mechanistic studies showed that DD1-induced apoptosis occurs through a novel caspase 2-mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. Interestingly, the cytotoxicity of NRIF3 and DD1 appears to be cell type specific, as they selectively kill breast cancer or related cells but not other examined cells of different origins. Our study demonstrates the feasibility of selectively inducing cytotoxicity in a specific cancer and suggests that breast cancer cells contain a novel "death switch" that can be specifically triggered by NRIF3 or DD1. Strategies utilizing NRIF3 and/or DD1 and/or targeting this death switch may lead to the development of novel and more selective therapeutics against breast cancer.

* Corresponding author. Mailing address: Department of Pharmacology, MSB 424, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-6279 Fax: (212) 263-7133. E-mail for Dangsheng Li: lid01{at}med.nyu.edu. E-mail for Herbert H. Samuels: herbert.samuels{at}med.nyu.edu.

Molecular and Cellular Biology, May 2004, p. 3838-3848, Vol. 24, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.9.3838-3848.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tinnikov, A. A., Yeung, K. T., Das, S., Samuels, H. H. (2009). Identification of a Novel Pathway That Selectively Modulates Apoptosis of Breast Cancer Cells. Cancer Res. 69: 1375-1382 [Abstract] [Full Text]  
  • Garapaty, S., Mahajan, M. A., Samuels, H. H. (2008). Components of the CCR4-NOT Complex Function as Nuclear Hormone Receptor Coactivators via Association with the NRC-interacting Factor NIF-1. J. Biol. Chem. 283: 6806-6816 [Abstract] [Full Text]  
  • Das, S., Nwachukwu, J. C., Li, D., Vulin, A. I., Martinez-Caballero, S., Kinnally, K. W., Samuels, H. H. (2007). The Nuclear Receptor Interacting Factor-3 Transcriptional Coregulator Mediates Rapid Apoptosis in Breast Cancer Cells through Direct and Bystander-Mediated Events. Cancer Res. 67: 1775-1782 [Abstract] [Full Text]  
  • Demaria, S., Santori, F. R., Ng, B., Liebes, L., Formenti, S. C., Vukmanovic, S. (2005). Select forms of tumor cell apoptosis induce dendritic cell maturation. J. Leukoc. Biol. 77: 361-368 [Abstract] [Full Text]  


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