| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Laboratories of Virology and
* Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, 00158 Rome, Italy
1Correspondence: Laboratory of Virology, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, 00158 Rome, Italy. E-mail venuti{at}ifo.it
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 ETBR mRNA and didn’t secrete ET-1. Binding studies showed that HPV-associated cells expressed an increased number of functional ETAR. ET-1 stimulated a marked dose-dependent increase in [3H]-thymidine incorporation with respect to the normal cells whereas ET-3 and ETBR agonists had no effect. In HPV-positive cancer cells, a specific antagonist of ETAR inhibited the proliferation induced by ET-1 and substantially reduced the basal growth rate of unstimulated cervical tumor 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 are increased and could be targeted 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.
Key Words: ETAR antagonists • genital tumors • tumor growth • papillomavirus • autocrine loop
This article has been cited by other articles:
|
|
 |
|
  L. E. Kandalaft, A. Facciabene, R. J. Buckanovich, and G. Coukos Endothelin B Receptor, a New Target in Cancer Immune Therapy Clin. Cancer Res., July 15, 2009; 15(14): 4521 - 4528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rosano, V. Di Castro, F. Spinella, M. R. Nicotra, P. G. Natali, and A. Bagnato ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo Mol. Cancer Ther., July 1, 2007; 6(7): 2003 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bagnato, F. Spinella, and L. Rosano Emerging role of the endothelin axis in ovarian tumor progression Endocr. Relat. Cancer, December 1, 2005; 12(4): 761 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Spinella, L. Rosano, V. Di Castro, M. R. Nicotra, P. G. Natali, and A. Bagnato Inhibition of Cyclooxygenase-1 and -2 Expression by Targeting the Endothelin A Receptor in Human Ovarian Carcinoma Cells Clin. Cancer Res., July 15, 2004; 10(14): 4670 - 4679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Ryan, N. J. Vogelzang, E. E. Vokes, H. L. Kindler, S. D. Undevia, R. Humerickhouse, A. K. Andre, Q. Wang, R. A. Carr, and M. J. Ratain Dose-Ranging Study of the Safety and Pharmacokinetics of Atrasentan in Patients with Refractory Malignancies Clin. Cancer Res., July 1, 2004; 10(13): 4406 - 4411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Spinella, L. Rosano, V. Di Castro, M. R. Nicotra, P. G. Natali, and A. Bagnato Endothelin-1 Decreases Gap Junctional Intercellular Communication by Inducing Phosphorylation of Connexin 43 in Human Ovarian Carcinoma Cells J. Biol. Chem., October 17, 2003; 278(42): 41294 - 41301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Zonnenberg, G. Groenewegen, T. J. Janus, T. W. Leahy, R. A. Humerickhouse, J. D. Isaacson, R. A. Carr, and E. Voest Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Atrasentan: An Endothelin Receptor Antagonist for Refractory Prostate Cancer Clin. Cancer Res., August 1, 2003; 9(8): 2965 - 2972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rosano, F. Spinella, D. Salani, V. Di Castro, A. Venuti, M. R. Nicotra, P. G. Natali, and A. Bagnato Therapeutic Targeting of the Endothelin A Receptor in Human Ovarian Carcinoma Cancer Res., May 15, 2003; 63(10): 2447 - 2453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Carducci, R. J. Padley, J. Breul, N. J. Vogelzang, B. A. Zonnenberg, D. D. Daliani, C. C. Schulman, A. A. Nabulsi, R. A. Humerickhouse, M. A. Weinberg, et al. Effect of Endothelin-A Receptor Blockade With Atrasentan on Tumor Progression in Men With Hormone-Refractory Prostate Cancer: A Randomized, Phase II, Placebo-Controlled Trial J. Clin. Oncol., February 15, 2003; 21(4): 679 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bagnato, A. Cirilli, D. Salani, P. Simeone, A. Muller, M. R. Nicotra, P. G. Natali, and A. Venuti Growth Inhibition of Cervix Carcinoma Cells in Vivo by Endothelin A Receptor Blockade Cancer Res., November 15, 2002; 62(22): 6381 - 6384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Carducci, J. B. Nelson, M. Kathy Bowling, T. Rogers, M. A. Eisenberger, V. Sinibaldi, R. Donehower, T. L. Leahy, R. A. Carr, J. D. Isaacson, et al. Atrasentan, an Endothelin-Receptor Antagonist for Refractory Adenocarcinomas: Safety and Pharmacokinetics J. Clin. Oncol., April 15, 2002; 20(8): 2171 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bagnato, L. Rosano, V. Di Castro, A. Albini, D. Salani, M. Varmi, M. R. Nicotra, and P. G. Natali Endothelin Receptor Blockade Inhibits Proliferation of Kaposi's Sarcoma Cells Am. J. Pathol., March 1, 2001; 158(3): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
