Expression profiling of nuclear receptors in the NCI60 cancer cell panel reveals receptor-drug and receptor-gene interactions

Susan Holbeck, Jianjun Chang, Anne M. Best, Angie L. Bookout, David J. Mangelsdorf, Elisabeth D. Martinez

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

We profiled the expression of the 48 human nuclear receptors (NRs) by quantitative RT-PCR in 51 human cancer cell lines of the NCI60 collection derived from nine different tissues. NR mRNA expression accurately classified melanoma, colon, and renal cancers, whereas lung, breast, prostate, central nervous system, and leukemia cell lines exhibited heterogeneous receptor expression. Importantly, receptor mRNA levels faithfully predicted the growth-inhibitory qualities of receptor ligands in nonendocrine tumors. Correlation analysis using NR expression profiles and drug response information across the cell line panel uncovered a number of new potential receptor-drug interactions, suggesting that in these cases, individual receptor levels may predict response to chemotherapeutic interventions. Similarly, by cross-comparing receptor levels within our expression dataset and relating these profiles to existing microarray gene expression data, we defined interactions among receptors and between receptors and other genes that can now be mechanistically queried. This work supports the strategy of using NR expression profiling to classify various types of cancer, define NR-drug interactions and receptor-gene networks, predict cancer-drug sensitivity, and identify druggable targets that may be pharmacologically manipulated for potential therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1287-1296
Number of pages10
JournalMolecular Endocrinology
Volume24
Issue number6
DOIs
StatePublished - Jun 2010

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Drug Receptors
Cytoplasmic and Nuclear Receptors
Genes
Neoplasms
Drug Interactions
Cell Line
Messenger RNA
Kidney Neoplasms
Gene Regulatory Networks
Pharmaceutical Preparations
Colonic Neoplasms
Prostate
Melanoma
Lung Neoplasms
Leukemia
Breast
Central Nervous System
Ligands
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Expression profiling of nuclear receptors in the NCI60 cancer cell panel reveals receptor-drug and receptor-gene interactions. / Holbeck, Susan; Chang, Jianjun; Best, Anne M.; Bookout, Angie L.; Mangelsdorf, David J.; Martinez, Elisabeth D.

In: Molecular Endocrinology, Vol. 24, No. 6, 06.2010, p. 1287-1296.

Research output: Contribution to journalArticle

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