Human papillomaviruses (HPVs) 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. HPV-positive cancer cells secrete ET-1 and express mRNA for ET-1 and its receptors, whereas HPV-negative carcinoma cell lines express only the ETB receptor (ETBR) mRNA and do not secrete ET-1. In HPV-positive cancer cells, ETAR mediates the ET-1-induced mitogenic effect and sustains the basal growth rate of unstimulated cervical tumour cells. Therefore, ET-1 may be involved in the neoplastic growth of HPV-associated cervical carcinoma, where the increased ET-1 autocrine loop can be targeted for antitumour therapy. In the present work, the action of specific antagonists of ETAR (BQ-123 and ABT-627), was analysed in CaSki and C33A cells that are derived from human cervical carcinoma. CaSki cells are HPV-16-positive, produce ET-1 and posses ETAR and ETBR, whereas the C33A line is HPV-negative, does not secrete ET-1 and has no ETAR. In HPV-positive cancer cells ABT-627 strongly inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated cervical tumour cells, whereas the ETBR antagonist had no effect. These results demonstrate that ET-1 participates in the progression of neoplastic growth in HPV-associated carcinoma, in which ETAR expression is increased and could be targeted for antitumour therapy. In conclusion, an ET-1 autocrine loop is involved in tumour cell proliferation via ETAR, and ABT-627 is effective in controlling proliferation of cervical carcinoma cells.
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September 2002
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Conference Article|
September 01 2002
Endothelin receptor blockade inhibits the growth of human papillomavirus-associated cervical carcinoma
Aldo VENUTI;
*Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
Dr A. Venuti (e-mail [email protected]).
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Debora SALANI;
Debora SALANI
†Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Alessia CIRILLI;
Alessia CIRILLI
*Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Paola SIMEONE;
Paola SIMEONE
*Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Antonio MULLER;
Antonio MULLER
*Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Silvio FLAMINI;
Silvio FLAMINI
*Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Robert PADLEY;
Robert PADLEY
‡Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064-6181, U.S.A.
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Anna BAGNATO
Anna BAGNATO
†Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 310S–313S.
Citation
Aldo VENUTI, Debora SALANI, Alessia CIRILLI, Paola SIMEONE, Antonio MULLER, Silvio FLAMINI, Robert PADLEY, Anna BAGNATO; Endothelin receptor blockade inhibits the growth of human papillomavirus-associated cervical carcinoma. Clin Sci (Lond) 1 September 2002; 103 (s2002): 310S–313S. doi: https://doi.org/10.1042/CS103S310S
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