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Am J Cancer Res. 2015 Feb 15;5(3):1117-23. eCollection 2015.

Correlated expression levels of endothelin receptor B and Plexin C1 in melanoma.

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Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan ; Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai-shi, Aichi 487-8501, Japan.
Department of Applied Biological Chemistry, Graduate School of Horticulture, Chiba University 648 Matsudo, Matsudo-shi, Chiba 271-8510, Japan.
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University Kumamoto 860-8556, Japan.
Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University Kasugai-shi, Aichi 487-8501, Japan.
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto 602-8566, Japan.


Discussion concerning the effect of endothelin receptor B (Ednrb) on melanoma continues because Ednrb has been reported to have both tumor promoting and suppressive effects for melanoma. In order to examine Ednrb-related signaling in melanomagenesis, DNA microarray analysis for a melanoma from a RFP/RET-transgenic mouse (RET-mouse) and a melanoma from an Ednrb-heterozygously deleted RET-mouse [Ednrb(+/-);RET-mouse], in both of which melanoma spontaneously develops, was performed in this study. We found that the expression level of Plexin C1 (PlxnC1), a suppressor for melanoma, in a melanoma from an Ednrb(+/-);RET-mouse was drastically decreased compared to that in a melanoma from a RET-mouse. Therefore, we further examined the correlation between Ednrb and PlxnC1 expression levels in melanomas. PlxnC1 transcript expression levels in melanomas from Ednrb(+/-);RET-mice were lower than those in melanomas from RET-mice. A strong correlation between Ednrb and PlxnC1 transcript expression levels (R = 0.78, p < 0.01) was also found in melanomas from both RET-mice and Ednrb(+/-);RET-mice. Correspondingly, there was a significant correlation between transcript (R = 0.80; p < 0.01) and protein (R = 0.60; p < 0.01) expression levels of EDNRB and PLXNC1 in human primary melanomas. Together with our results showing that the expression level of PLXNC1 transcript was reduced in EDNRB-depleted human melanoma cells, our results showing positively correlated expression levels of Ednrb/EDNRB and PlxnC1/PLXNC1 in melanoma suggest that PlxnC1/PLXNC1 is involved in the Ednrb/EDNRB-mediated suppressive effect on melanoma.


Ednrb; Plexin C1; melanoma


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