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.