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

Biochemical and Biophysical Research Communications
Keiji TaneseMichiie Sakamoto

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 0.8kb 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.

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Citations

Mar 10, 2016·Pharmacological Reviews·Anthony P DavenportJanet J Maguire
Jan 15, 2011·British Journal of Pharmacology·A BagnatoJ Growcott
Jul 3, 2013·Molecular Carcinogenesis·Shaolin NieJianping Zhou
Jan 22, 2015·Genesis : the Journal of Genetics and Development·Joseph A CacioppoCheMyong Ko
Apr 7, 2012·Life Sciences·Janet J MaguireAnthony P Davenport
Jul 26, 2013·Nature Reviews. Cancer·Laura RosanòAnna Bagnato

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