Research resource

Diagnostic and therapeutic potential of nuclear receptor expression in lung cancer

Yangsik Jeong, Yang Xie, Woochang Lee, Angie L. Bookout, Luc Girard, Gabriela Raso, Carmen Behrens, Ignacio I. Wistuba, Adi F. Gadzar, John D. Minna, David J. Mangelsdorf

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Lung cancer is the leading cause of cancer-related death. Despite a number of studies that have provided prognostic biomarkers for lung cancer, a paucity of reliable markers and therapeutic targets exist to diagnose and treat this aggressive disease. In this study we investigated the potential of nuclear receptors (NRs), many of which are well-established drug targets, as therapeutic markers in lung cancer. Using quantitative real-time PCR, we analyzed the expression of the 48 members of the NR superfamily in a human panel of 55 normal and lung cancer cell lines. Unsupervised cluster analysis of the NR expression profile segregated normal from tumor cell lines and grouped lung cancers according to type (i.e. small vs. non-small cell lung cancers). Moreover, we found that the NR signature was 79% accurate in diagnosing lung cancer incidence in smokers (n 129). Finally, the evaluation of a subset of NRs (androgen receptor, estrogen receptor, vitamin D receptor, and peroxisome proliferator-activated receptor-γ) demonstrated the therapeutic potential of using NR expression to predict ligand-dependent growth responses in individual lung cancer cells. Preclinical evaluation of one of these receptors (peroxisome proliferator activated receptor-γ) in mouse xenografts confirmed that ligand-dependent inhibitory growth responses in lung cancer can be predicted based on a tumor's receptor expression status. Taken together, this study establishes NRs as theragnostic markers for predicting lung cancer incidence and further strengthens their potential as therapeutic targets for individualized treatment.

Original languageEnglish (US)
Pages (from-to)1443-1454
Number of pages12
JournalMolecular Endocrinology
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2012

Fingerprint

Cytoplasmic and Nuclear Receptors
Lung Neoplasms
Research
Peroxisome Proliferator-Activated Receptors
Therapeutics
Ligands
Calcitriol Receptors
Incidence
Androgen Receptors
Growth
Tumor Cell Line
Heterografts
Non-Small Cell Lung Carcinoma
Estrogen Receptors
Cluster Analysis
Real-Time Polymerase Chain Reaction
Neoplasms
Biomarkers
Cell Line
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Research resource : Diagnostic and therapeutic potential of nuclear receptor expression in lung cancer. / Jeong, Yangsik; Xie, Yang; Lee, Woochang; Bookout, Angie L.; Girard, Luc; Raso, Gabriela; Behrens, Carmen; Wistuba, Ignacio I.; Gadzar, Adi F.; Minna, John D.; Mangelsdorf, David J.

In: Molecular Endocrinology, Vol. 26, No. 8, 01.08.2012, p. 1443-1454.

Research output: Contribution to journalArticle

Jeong, Yangsik ; Xie, Yang ; Lee, Woochang ; Bookout, Angie L. ; Girard, Luc ; Raso, Gabriela ; Behrens, Carmen ; Wistuba, Ignacio I. ; Gadzar, Adi F. ; Minna, John D. ; Mangelsdorf, David J. / Research resource : Diagnostic and therapeutic potential of nuclear receptor expression in lung cancer. In: Molecular Endocrinology. 2012 ; Vol. 26, No. 8. pp. 1443-1454.
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