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 language | English |
|---|---|
| Pages (from-to) | 486-491 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 391 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Jan 1 |
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Keywords
- Basal cell carcinoma
- Endothelin-2
- Hedgehog signaling
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
Cite this
Endothelin-2 is upregulated in basal cell carcinoma under control of Hedgehog signaling pathway. / Tanese, Keiji; Fukuma, Mariko; Ishiko, Akira; Sakamoto, Michiie.
In: Biochemical and Biophysical Research Communications, Vol. 391, No. 1, 01.01.2010, p. 486-491.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelin-2 is upregulated in basal cell carcinoma under control of Hedgehog signaling pathway
AU - Tanese, Keiji
AU - Fukuma, Mariko
AU - Ishiko, Akira
AU - Sakamoto, Michiie
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Basal cell carcinoma
KW - Endothelin-2
KW - Hedgehog signaling
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U2 - 10.1016/j.bbrc.2009.11.085
DO - 10.1016/j.bbrc.2009.11.085
M3 - Article
C2 - 19914214
AN - SCOPUS:72949095648
VL - 391
SP - 486
EP - 491
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -