Steroid Receptor and Growth Factor Receptor Expression in Human Nonsmall Cell Lung Cancers Using Cells Procured by Laser-capture Microdissection

  • Alan KerrII
  • James F. Eliason
  • James L. Wittliff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)


Few biomarkers exist for management of nonsmall cell lung cancers (NSCLC), although estrogen receptor (ERα and ERβ) and EGF receptor (EGFR) expression has been related to clinical outcome (1–6). To circumvent problems of cellular heterogeneity in whole tissue, relative gene expression of ERα, ERβ, EGFR, and HER-2 (c-erb-B2) was examined in pure lung carcinoma (LC) cells and normal epithelia by LCM. Cell-specific RNA was isolated and purified for RT-qPCR and microarray. Comparison of NSCLC cells to normal epithelia indicated increased levels of mRNA expression of ERβ, ERα, EGFR, and HER-2 by 31%, 38%, 54%, and 62%, respectively, in LCs. The majority of NSCLC exhibiting low ERα and high HER-2 expression were from smokers. Although there was no correlation between ERβ or EGFR expression and smoking history, there appeared to be an inverse relationship between levels of ERβ and EGFR mRNAs in normal and neoplastic lung. Additionally, microarray analyses of LCM cells revealed >2,000 genes significantly altered in LC compared with normal epithelia. Herein, differences in NSCLC gene expression and normal lung cells were noted between specimens from gender and smoking groups. Microarray data revealed ERα expression was associated with alterations in <20 genes while ERβ expression revealed >500 associated genes, suggesting a more prominent role for ERβ in lung. HER-2 mRNA levels appeared associated with >1,000 genes, while EGFR mRNA levels were associated with far fewer genes. Collectively, results suggest quantitative genomic analyses of pure cell populations allow more accurate interpretation of LC status, which is being correlated with clinical outcome.


NSCLC Cell Normal Epithelium Global Gene Expression Profile Human Nonsmall Cell Lung Cancer Growth Factor Receptor Expression 
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  1. 1.
    Su JM, Hsu HK, Chang H, et al. (1996) Expression of estrogen and progesterone receptors in non-small-cell lung cancer: immunohistochemical study. Anticancer Res 16(6B):3803–6.PubMedGoogle Scholar
  2. 2.
    Fasco MJ, Hurteau GJ, Spivack SD (2002) Gender-dependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue. Mol Cell Endocrinol 188(1–2):125–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Stabile LP, Davis AL, Gubish CT, et al. (2002) Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res 62(7):2141–50.PubMedGoogle Scholar
  4. 4.
    Kawai H, Ishii A, Washiya K, et al. (2005) Combined overexpression of EGFR and estrogen receptor alpha correlates with a poor outcome in lung cancer. Anticancer Res 25(6C):4693–8.PubMedGoogle Scholar
  5. 5.
    Kawai H, Ishii A, Washiya K, et al. (2005) Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer. Clin Cancer Res 11(14):5084–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Schwartz AG, Prysak GM, Murphy V, et al. (2005) Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex. Clin Cancer Res 11(20):7280–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Fitzpatrick SL, Brightwell J, Wittliff JL, et al. (1984) Epidermal growth factor binding by breast tumor biopsies and relationship to estrogen receptor and progestin receptor levels. Cancer Res 44(8):3448–53.PubMedGoogle Scholar
  8. 8.
    Fekete M, Wittliff JL, Schally AV (1989) Characteristics and distribution of receptors for [D-TRP6]-luteinizing hormone-releasing hormone, somatostatin, epidermal growth factor, and sex steroids in 500 biopsy samples of human breast cancer. J Clin Lab Anal 3(3):137–47.PubMedCrossRefGoogle Scholar
  9. 9.
    Gee JM, Harper ME, Hutcheson IR, et al. (2003) The antiepidermal growth factor receptor agent gefitinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitro. Endocrinology 144(11):5105–17.PubMedCrossRefGoogle Scholar
  10. 10.
    Hutcheson IR, Knowlden JM, Madden TA, et al. (2003) Oestrogen receptor-mediated modulation of the EGFR/MAPK pathway in tamoxifen-resistant MCF-7 cells. Breast Cancer Res Treat 81(1):81–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Levin ER (2003) Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 17(3):309–17.PubMedCrossRefGoogle Scholar
  12. 12.
    Nicholson RI, Hutcheson IR, Britton D, et al. (2005) Growth factor signalling networks in breast cancer and resistance to endocrine agents: new therapeutic strategies. J Steroid Biochem Mol Biol 93(2–5):257–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Wittliff JL, Durant JR, Fisher B (1981) Methods of steroid receptor analyses and their quality control in the clinical laboratory. Prog Clin Biol Res 74:397–411.PubMedGoogle Scholar
  14. 14.
    Wittliff JL, Kunitake ST, Chu SS, Travis JC (2000) Applications of laser capture microdissection in genomics and proteomics. J Clin Ligand Assay 23:66–73.Google Scholar
  15. 15.
    Wittliff JL, Erlander MG (2002) Laser capture microdissection and its applications in genomics and proteomics. Methods Enzymol 356:12–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Alan KerrII
    • 1
  • James F. Eliason
  • James L. Wittliff
    • 1
  1. 1.Hormone Receptor Laboratory Department of Biochemistry and MolecularBiology University of Louisville - HSCLouisvilleUSA

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