The zinc metalloprotease, endothelin-converting enzyme-1 (ECE-1), which converts the mitogenic peptide endothelin-1 (ET-1) from its biologically inactive precursor big-ET-1, is commonly upregulated in prostate cancer (PC) cells.
NEP normally functions to inactivate peptides such as bombesin and endothelin-1, and potentiates the effects of the PTEN tumor suppressor via a direct protein-protein interaction.NEP loss contributes to PC progression.
Considering that endothelin-1 induces apoptosis in melanoma cells and that silencing of endothelin receptor B is observed in prostate cancers, its reduced expression was speculated to confer a growth advantage to lung cancer cells.
In conclusion, ET-1 production by prostate adenocarcinoma cells is down-regulated by androgens and up-regulated by factors involved in tumour progression indicating a role for this peptide in the biology of prostate cancer.
The inhibition could be neutralized by specific ET-1 antibody, indicating the association of prostate cancer-derived ET-1 with inhibition of bone resorption.
Endothelin-1 (ET-1) is not only a potent vasoconstrictor but also serves as an important growth stimulator in various cancers, including breast, cervical, pancreatic, and prostate cancer.