Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer

  • Authors:
    • Lucy J. Knight
    • Joseph Burrage
    • Sarah R. Bujac
    • Carolyn Haggerty
    • Alexander Graham
    • Neil J. Gibson
    • Gillian Ellison
    • James W. Growcott
    • A. Nigel Brooks
    • Andrew M. Hughes
    • George Xinarianos
    • Georgios Nikolaidis
    • John K. Field
    • Triantafillos Liloglou
  • View Affiliations

  • Published online on: February 1, 2009     https://doi.org/10.3892/ijo_00000171
  • Pages: 465-471
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Endothelin-1 is overexpressed in several tumor types. Activation of the endothelin-A (ETA) receptor may promote cell growth, angiogenesis and invasion, and inhibits the apoptotic process, while activation of the endothelin-B (ETB) receptor may induce cell death by apoptosis and inhibit tumor progression. Hypermethylation and subsequent silencing of the ETB receptor gene promoter has been reported in some cancer types. As the endothelin pathway is subject to research for pharmacological cancer treatment, we investigated the extent of epigenetic deregulation of the ETB receptor gene in non-small cell lung cancer (NSCLC). We scanned 64 NSCLC paired tumor/normal surgical specimens for the ETB receptor promoter for methylation by developing four pyrosequencing assays that covered 24 CpGs. The ETB receptor promoter was significantly hypermethylated in 31 (48%) of tumor samples, presenting considerably higher methylation in 22/24 CpG sites compared with the normal counterpart tissues. ETB receptor mRNA levels were reduced in all lung tumors compared with normal adjacent lung tissue, indicating the potentially important involvement of this gene in lung cancer development. Furthermore, tumor samples with ETB receptor gene methylation tended to have lower receptor mRNA levels compared with unmethylated tumor specimens, suggesting a primary epigenetic role in ETB receptor silencing. Our results point to a significant involvement of ETB receptor epigenetic deregulation in the pathogenesis of lung cancer making the gene a promising candidate biomarker for response to regimens modulating the endothelin axis.

Related Articles

Journal Cover

February 2009
Volume 34 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Knight, L.J., Burrage, J., Bujac, S.R., Haggerty, C., Graham, A., Gibson, N.J. ... Liloglou, T. (2009). Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer. International Journal of Oncology, 34, 465-471. https://doi.org/10.3892/ijo_00000171
MLA
Knight, L. J., Burrage, J., Bujac, S. R., Haggerty, C., Graham, A., Gibson, N. J., Ellison, G., Growcott, J. W., Brooks, A. N., Hughes, A. M., Xinarianos, G., Nikolaidis, G., Field, J. K., Liloglou, T."Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer". International Journal of Oncology 34.2 (2009): 465-471.
Chicago
Knight, L. J., Burrage, J., Bujac, S. R., Haggerty, C., Graham, A., Gibson, N. J., Ellison, G., Growcott, J. W., Brooks, A. N., Hughes, A. M., Xinarianos, G., Nikolaidis, G., Field, J. K., Liloglou, T."Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer". International Journal of Oncology 34, no. 2 (2009): 465-471. https://doi.org/10.3892/ijo_00000171