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  • Oncogenomics
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Microarray analysis uncovers retinoid targets in human bronchial epithelial cells

Oncogene volume 22, pages 4924–4932 (2003)Cite this article

Abstract

Retinoids, the natural and synthetic derivatives of vitamin A, have a role in cancer treatment and prevention. There is a need to reveal mechanisms that account for retinoid response or resistance. This study identified candidate all-trans-retinoic acid (RA) target genes linked to growth suppression in BEAS-2B human bronchial epithelial cells. Microarray analyses were performed using Affymetrix arrays. A total of 11 RA-induced species were validated by reverse transcription polymerase chain reaction (RT-PCR), Western or Northern analyses. Three of these species were novel candidate RA-target genes in human bronchial epithelial cells. These included: placental bone morphogenetic protein (PLAB), polyamine oxidase isoform 1 (PAOh1) and E74-like factor 3 (ELF3). Expression patterns were studied in RA-resistant BEAS-2B-R1 cells. In BEAS-2B-R1 cells, RA dysregulated the expression of the putative lymphocyte G0/G1 switch gene (G0S2), heme oxygenase 1 (HMOX1), tumor necrosis factor-α-induced protein 2 (TNFAIP2), inhibitor of DNA binding 1(Id1), fos-like antigen 1 (FOSL1), transglutaminase 2 (TGM2), asparagine synthetase (ASNS), PLAB, PAOh1 and ELF3, while prominent induction of insulin-like growth-factor-binding protein 6 (IGFBP6) still occurred. In summary, this study identified 11 candidate RA-target genes in human bronchial epithelial cells including three novel species. Expression studies in BEAS-2B-R1 cells indicated that several were directly implicated in RA signaling, since their aberrant expression was linked to RA resistance of human bronchial epithelial cells.

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Acknowledgements

We thank Dr. Vishva Dixit (University of Michigan Medical School) for providing the anti-B94/TNFAIP2 antibody. We thank Dr. Michael Spinella and Dr. James DiRenzo (Dartmouth Medical School) for helpful discussions. This work was supported by the National Institutes of Health grant R01-CA87546 (ED), American Cancer Society Research Grant RPG-90-019-10-DDC (ED), a research grant from Pfizer (ED), a research grant from the Samuel Waxman Foundation (ED), and the Oracle Giving Funding (ED). KHD was supported by the American Society of Clinical Oncology (ASCO) Young Investigator Award and SJF was supported by a Lance Armstrong Foundation Award.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, 03755, NH, USA

    Yan Ma, Haoning Fu, Konstantin H Dragnev, Sarah J Freemantle & Ethan Dmitrovsky

  2. Department of Medicine, Dartmouth Medical School, Hanover, 03755, NH, USA

    Konstantin H Dragnev & Ethan Dmitrovsky

  3. Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, 03755, NH, USA

    Konstantin H Dragnev & Ethan Dmitrovsky

  4. Pfizer Global Research and Development, Groton, 06340, CT, USA

    Petra H Koza-Taylor, Debra A DiMattia, Lynn Hames, Tom Turi & Jean S Beebe

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  1. Yan Ma
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Correspondence to Ethan Dmitrovsky.

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Ma, Y., Koza-Taylor, P., DiMattia, D. et al. Microarray analysis uncovers retinoid targets in human bronchial epithelial cells. Oncogene 22, 4924–4932 (2003). https://doi.org/10.1038/sj.onc.1206728

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