Endothelin-2 is upregulated in basal cell carcinoma under control of Hedgehog signaling pathway

Keiji Tanese, Mariko Fukuma, Akira Ishiko, Michiie Sakamoto

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Vasoactive peptide endothelins are a group of small peptides with diverse paracrine/autocrine actions and are reported to be involved in the pathogenesis of many human malignancies. Basal cell carcinoma (BCC) is a common malignant skin tumor that frequently has aberrant activation of the Hedgehog (HH) signaling pathway. We show here that endothelin-2 (ET-2) is overexpressed in BCC under the control of HH signaling. By real-time quantitative RT-PCR analysis, significant expression of ET-2 mRNA was observed in 19 of 20 cases (95%) compared to normal skin. In addition, inhibition of the HH signaling pathway in a mouse BCC cell line downregulated endogenous ET-2, and activation of HH signaling in mouse embryonic fibroblast upregulated endogenous ET-2. Moreover, the 3′ promoter region of ET-2 gene contains the GLI-binding site and a 0.8 kb downstream fragment containing GLI-binding sites activates transcription in a reporter assay. These data indicate that ET-2 is a direct target gene of HH signaling in BCC.

Original languageEnglish
Pages (from-to)486-491
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

Keywords

  • Basal cell carcinoma
  • Endothelin-2
  • Hedgehog signaling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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