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

Aldo Venuti, Debora Salani, Vanessa Manni, Federica Poggiali, Anna Bagnato

Research output: Contribution to journalArticlepeer-review

Abstract

Human papillomaviruses (HPV) are associated with cervical cancer and interact with growth factors that may enhance malignant transformation of cervical carcinoma cells. Endothelin-1 (ET-1) is released from HPV transfected keratinocytes and induces increased growth response in these cell lines in comparison 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 cancer cells secreted ET-1 and expressed mRNA for ET-1 and its receptors, whereas a HPV-negative carcinoma cell line expressed only the ET(B)R mRNA and didn't secrete ET-1. Binding studies showed that HPV-associated cells expressed an increased number of functional ET(A)R. ET-1 stimulated a marked dose-dependent increase in [3H]-thymidine incorporation with respect to the normal cells whereas ET-3 and ET(B)R agonists had no effect. In HPV-positive cancer cells, a specific antagonist of ET(A)R inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated cervical tumor cells, whereas the ET(B)R antagonist had no effect. These results demonstrate that ET-1 participates in the progression of neoplastic growth in HPV-associated carcinoma, in which ET(A)R are increased and could be targeted for antitumor therapy.

Original languageEnglish
Pages (from-to)2277-2283
Number of pages7
JournalFASEB Journal
Volume14
Issue number14
Publication statusPublished - 2000

Keywords

  • Autocrine loop
  • ET(A)R antagonists
  • Genital tumors
  • Papillomavirus
  • Tumor growth

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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