TR3/Nur77 in colon cancer cell apoptosis

Andrew J. Wilson, Diego Arango, John M. Mariadason, Barbara G. Heerdt, Leonard H. Augenlicht

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The orphan nuclear receptor TR3/Nur77 has emerged as a viable candidate in the coordinate regulation of cell proliferation and apoptosis, essential for maintaining normal architecture in rapidly renewing tissues such as the colonic mucosa. TR3 induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. Here we report a distinctly different mechanism of TR3-mediated apoptosis in colon cancer cells. Nucleus-to-cytoplasm translocation of a green fluorescent protein-TR3 construct, but not its direct mitochondrial targeting, was associated with apoptosis induced by the short-chain fatty acid, butyrate. Similar results were observed for the nonsteroidal anti-inflammatory drug, sulindac, and the chemotherapeutic drug, 5-fluorouracil. A mutant TR3 construct lacking DNA-binding ability exerted a potent proapoptotic effect in colon cancer cells that was associated with cytochrome c release, an action dependent upon cytoplasmic localization of the construct, but, again, not its direct mitochondrial targeting. We identified a potential role for BAX recruitment to the mitochondria, secondary to cytoplasmic translocation of TR3, in inducing cytochrome c release and in mediating apoptosis. Therefore, TR3 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria.

Original languageEnglish (US)
Pages (from-to)5401-5407
Number of pages7
JournalCancer Research
Volume63
Issue number17
StatePublished - Sep 1 2003

Fingerprint

Colonic Neoplasms
Apoptosis
Cytochromes c
Mitochondria
Nuclear Receptor Subfamily 4, Group A, Member 1
Sulindac
Volatile Fatty Acids
Butyrates
Cell Lineage
Green Fluorescent Proteins
Fluorouracil
Pharmaceutical Preparations
Cytoplasm
Mucous Membrane
Anti-Inflammatory Agents
Cell Proliferation
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wilson, A. J., Arango, D., Mariadason, J. M., Heerdt, B. G., & Augenlicht, L. H. (2003). TR3/Nur77 in colon cancer cell apoptosis. Cancer Research, 63(17), 5401-5407.

TR3/Nur77 in colon cancer cell apoptosis. / Wilson, Andrew J.; Arango, Diego; Mariadason, John M.; Heerdt, Barbara G.; Augenlicht, Leonard H.

In: Cancer Research, Vol. 63, No. 17, 01.09.2003, p. 5401-5407.

Research output: Contribution to journalArticle

Wilson, AJ, Arango, D, Mariadason, JM, Heerdt, BG & Augenlicht, LH 2003, 'TR3/Nur77 in colon cancer cell apoptosis', Cancer Research, vol. 63, no. 17, pp. 5401-5407.
Wilson AJ, Arango D, Mariadason JM, Heerdt BG, Augenlicht LH. TR3/Nur77 in colon cancer cell apoptosis. Cancer Research. 2003 Sep 1;63(17):5401-5407.
Wilson, Andrew J. ; Arango, Diego ; Mariadason, John M. ; Heerdt, Barbara G. ; Augenlicht, Leonard H. / TR3/Nur77 in colon cancer cell apoptosis. In: Cancer Research. 2003 ; Vol. 63, No. 17. pp. 5401-5407.
@article{0d4f79d06eda413db500f5f37b788064,
title = "TR3/Nur77 in colon cancer cell apoptosis",
abstract = "The orphan nuclear receptor TR3/Nur77 has emerged as a viable candidate in the coordinate regulation of cell proliferation and apoptosis, essential for maintaining normal architecture in rapidly renewing tissues such as the colonic mucosa. TR3 induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. Here we report a distinctly different mechanism of TR3-mediated apoptosis in colon cancer cells. Nucleus-to-cytoplasm translocation of a green fluorescent protein-TR3 construct, but not its direct mitochondrial targeting, was associated with apoptosis induced by the short-chain fatty acid, butyrate. Similar results were observed for the nonsteroidal anti-inflammatory drug, sulindac, and the chemotherapeutic drug, 5-fluorouracil. A mutant TR3 construct lacking DNA-binding ability exerted a potent proapoptotic effect in colon cancer cells that was associated with cytochrome c release, an action dependent upon cytoplasmic localization of the construct, but, again, not its direct mitochondrial targeting. We identified a potential role for BAX recruitment to the mitochondria, secondary to cytoplasmic translocation of TR3, in inducing cytochrome c release and in mediating apoptosis. Therefore, TR3 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria.",
author = "Wilson, {Andrew J.} and Diego Arango and Mariadason, {John M.} and Heerdt, {Barbara G.} and Augenlicht, {Leonard H.}",
year = "2003",
month = "9",
day = "1",
language = "English (US)",
volume = "63",
pages = "5401--5407",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - TR3/Nur77 in colon cancer cell apoptosis

AU - Wilson, Andrew J.

AU - Arango, Diego

AU - Mariadason, John M.

AU - Heerdt, Barbara G.

AU - Augenlicht, Leonard H.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - The orphan nuclear receptor TR3/Nur77 has emerged as a viable candidate in the coordinate regulation of cell proliferation and apoptosis, essential for maintaining normal architecture in rapidly renewing tissues such as the colonic mucosa. TR3 induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. Here we report a distinctly different mechanism of TR3-mediated apoptosis in colon cancer cells. Nucleus-to-cytoplasm translocation of a green fluorescent protein-TR3 construct, but not its direct mitochondrial targeting, was associated with apoptosis induced by the short-chain fatty acid, butyrate. Similar results were observed for the nonsteroidal anti-inflammatory drug, sulindac, and the chemotherapeutic drug, 5-fluorouracil. A mutant TR3 construct lacking DNA-binding ability exerted a potent proapoptotic effect in colon cancer cells that was associated with cytochrome c release, an action dependent upon cytoplasmic localization of the construct, but, again, not its direct mitochondrial targeting. We identified a potential role for BAX recruitment to the mitochondria, secondary to cytoplasmic translocation of TR3, in inducing cytochrome c release and in mediating apoptosis. Therefore, TR3 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria.

AB - The orphan nuclear receptor TR3/Nur77 has emerged as a viable candidate in the coordinate regulation of cell proliferation and apoptosis, essential for maintaining normal architecture in rapidly renewing tissues such as the colonic mucosa. TR3 induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. Here we report a distinctly different mechanism of TR3-mediated apoptosis in colon cancer cells. Nucleus-to-cytoplasm translocation of a green fluorescent protein-TR3 construct, but not its direct mitochondrial targeting, was associated with apoptosis induced by the short-chain fatty acid, butyrate. Similar results were observed for the nonsteroidal anti-inflammatory drug, sulindac, and the chemotherapeutic drug, 5-fluorouracil. A mutant TR3 construct lacking DNA-binding ability exerted a potent proapoptotic effect in colon cancer cells that was associated with cytochrome c release, an action dependent upon cytoplasmic localization of the construct, but, again, not its direct mitochondrial targeting. We identified a potential role for BAX recruitment to the mitochondria, secondary to cytoplasmic translocation of TR3, in inducing cytochrome c release and in mediating apoptosis. Therefore, TR3 translocation from the nucleus may initiate the apoptotic cascade in colon cancer cells by stimulating other cytosolic proapoptotic molecules to associate with mitochondria.

UR - http://www.scopus.com/inward/record.url?scp=0141705418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141705418&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 5401

EP - 5407

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 17

ER -