Expression of endothelin 1 and endothelin A receptor in HPV-associated cervical carcinoma: new potential targets for anticancer therapy

Human papillomaviruses (HPV) are associated with cervical cancer and intera ct with growth factors that may enhance malignant transformation of cervica l carcinoma cells. Endothelin-1 (ET-1) is released from HPV transfected ker atinocytes and induces increased growth response in these cell lines in com parison with normal cells. In the present study several cervical carcinoma cell Lines have been analyzed to investigate the expression of ET-1 and its receptors as well as their involvement in tumor growth, All HPV-positive c ancer cells secreted ET-1 and expressed mRNA for ET-1 and its receptors, wh ereas a HPV-negative carcinoma cell line expressed only the ETBR mRNA and d idn't secrete ET-1, Binding studies showed that HPV-associated cells expres sed an increased number of functional ETAR. ET-1 stimulated a marked dose-d ependent increase in [H-3]-thymidine incorporation with respect to the norm al cells whereas ET-3 and ETBR agonists had no effect, In HPV-positive canc er cells, a specific antagonist of ETAR inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated ce rvical tumor cells, whereas the ETBR antagonist had no effect, These result s demonstrate that ET-1 participates in the progression of neoplastic growt h in HPV-associated carcinoma, in which ETAR are increased and could be tar geted for antitumor therapy.-Venuti, A., Salani, D., Manni, V., Poggiali, F ., Bagnato, A. Expression of endothelin 1 and endothelin A receptor in HPV- associated cervical carcinoma: new potential targets for anticancer therapy .