help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cassoni, P.
Right arrow Articles by Bussolati, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cassoni, P.
Right arrow Articles by Bussolati, G.
Endocrinology Vol. 142, No. 3 1130-1136
Copyright © 2001 by The Endocrine Society

ARTICLES

Activation of Functional Oxytocin Receptors Stimulates Cell Proliferation in Human Trophoblast and Choriocarcinoma Cell Lines1

Paola Cassoni, Anna Sapino, Luca Munaron, Silvia Deaglio, Bice Chini, Andrea Graziani, Asif Ahmed and Gianni Bussolati

Department of Biomedical Sciences and Oncology (P.C., A.S., G.B.), Department of Animal and Human Biology and National Institute for the Physics of Matter (L.M.), and Laboratory of Cell Biology, Department of Genetics (S.D.), University of Turin, 10126 Turin, Italy; Department of Medical Sciences, University of Novara (A.G.), 28100 Novara, Italy; Consiglio Nationale per le Ricerche Cellular and Molecular Pharmacology Center (B.C.), 20129 Milan, Italy; and Department of Reproductive and Vascular Biology, Division of Reproductive and Child Health, University of Birmingham (A.A.), Birmingham Women’s Hospital, Birmingham, B15 2TG, United Kingdom

Address all correspondence and requests for reprints to: Dr. Gianni Bussolati, Department of Biomedical Sciences and Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy. E-mail: bussola{at}molinette.unito.it

Despite oxytocin receptors (OTR) being present in human chorio-decidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [125I]oxytocin ([125I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH29]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
M. U. Baumann, S. Zamudio, and N. P. Illsley
Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is mediated by hypoxia-inducible factor-1
Am J Physiol Cell Physiol, July 1, 2007; 293(1): C477 - C485.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Reversi, V. Rimoldi, S. Brambillasca, and B. Chini
Effects of cholesterol manipulation on the signaling of the human oxytocin receptor
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R861 - R869.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Reversi, V. Rimoldi, T. Marrocco, P. Cassoni, G. Bussolati, M. Parenti, and B. Chini
The Oxytocin Receptor Antagonist Atosiban Inhibits Cell Growth via a "Biased Agonist" Mechanism
J. Biol. Chem., April 22, 2005; 280(16): 16311 - 16318.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
L. Vignozzi, G. B. Vannelli, A. Morelli, R. Mancina, M. Marini, P. Ferruzzi, C. Crescioli, M. Luconi, S. Donati, A. D. Fisher, et al.
Identification, characterization and biological activity of oxytocin receptor in the developing human penis
Mol. Hum. Reprod., February 1, 2005; 11(2): 99 - 106.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Jankowski, B. Danalache, D. Wang, P. Bhat, F. Hajjar, M. Marcinkiewicz, J. Paquin, S. M. McCann, and J. Gutkowska
Oxytocin in cardiac ontogeny
PNAS, August 31, 2004; 101(35): 13074 - 13079.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Matsuura, T. Nagai, N. Nishigaki, T. Oyama, J. Nishi, H. Wada, M. Sano, H. Toko, H. Akazawa, T. Sato, et al.
Adult Cardiac Sca-1-positive Cells Differentiate into Beating Cardiomyocytes
J. Biol. Chem., March 19, 2004; 279(12): 11384 - 11391.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Zhong, M. Yang, and B. M. Sanborn
Extracellular Signal-Regulated Kinase 1/2 Activation by Myometrial Oxytocin Receptor Involves G{alpha}qG{beta}{gamma} and Epidermal Growth Factor Receptor Tyrosine Kinase Activation
Endocrinology, July 1, 2003; 144(7): 2947 - 2956.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Pequeux, C. Breton, J.-C. Hendrick, M.-T. Hagelstein, H. Martens, R. Winkler, V. Geenen, and J.-J. Legros
Oxytocin Synthesis and Oxytocin Receptor Expression by Cell Lines of Human Small Cell Carcinoma of the Lung Stimulate Tumor Growth through Autocrine/Paracrine Signaling
Cancer Res., August 15, 2002; 62(16): 4623 - 4629.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Paquin, B. A. Danalache, M. Jankowski, S. M. McCann, and J. Gutkowska
Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes
PNAS, July 9, 2002; 99(14): 9550 - 9555.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Cassoni, A. Sapino, S. Deaglio, B. Bussolati, M. Volante, L. Munaron, A. Albini, A. Torrisi, and G. Bussolati
Oxytocin Is a Growth Factor for Kaposi's Sarcoma Cells: Evidence of Endocrine-Immunological Cross-Talk
Cancer Res., April 1, 2002; 62(8): 2406 - 2413.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Bussolati, M. Chinol, B. Chini, A. Nacca, P. Cassoni, and G. Paganelli
111In-labeled 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic Acid-Lys8-Vasotocin: A New Powerful Radioligand for Oxytocin Receptor-expressing Tumors
Cancer Res., June 1, 2001; 61(11): 4393 - 4397.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. Bussolati and P. Cassoni
Editorial: The Oxytocin/Oxytocin Receptor System--Expect the Unexpected
Endocrinology, April 1, 2001; 142(4): 1377 - 1379.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society