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Direct effect of a gonadotropin‐releasing hormone agonist on the growth of canine mammary tumour cells
Author(s) -
Pagnini Ugo,
Florio Salvatore,
Crispino Luca,
Pagnini Giuseppe,
Colangelo Donato,
Rocco Daniela,
Pacilio Carmen,
Pacilio Maria,
Macaluso Marcella,
Giordano Antonio
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10167
Subject(s) - epidermal growth factor , agonist , medicine , endocrinology , receptor , calcium in biology , intracellular , biology , gonadotropin releasing hormone , cell growth , downregulation and upregulation , chemistry , hormone , microbiology and biotechnology , luteinizing hormone , biochemistry , gene
Gonadotropin‐releasing hormone (GnRH) agonist exert “in vivo” an inhibitory action on the growth of hormone‐dependent canine mammary tumours (Lombardi et al. [1999] J. Vet. Pharmacol Ther. 22(1):56–61). The present experiments have been performed “in vitro” in order to investigate the mechanisms involved in this direct antiproliferative action of GnRH agonists. In particular, the aim was to study whether these compounds might exert their antiproliferative effect by interfering with the stimulatory action of epidermal growth factor (EGF). To this purpose, the effects of GnRH agonist, Goserelin (GnRH‐A), on the mitogenic action of EGF, on EGF‐activated intracellular signaling mechanisms (intracellular calcium and nitric oxide production) as well as on ATP induced cell proliferation and signalling, and on the binding of EGF receptors have been evaluated in primary culture of canine mammary tumour cells. The results of these “in vitro” studies show that GnRH‐A counteracts the mitogenic action of EGF and ATP, decreases the EGF/ATP‐induced calcium signalling and reduces EGF binding, probably by means of NO‐induced [Ca 2+ ] i downregulation. These data suggest that GnRH agonists may inhibit the proliferation of the tumour cells by interfering with the stimulatory action of EGF. J. Cell. Biochem. 85: 470–481, 2002. © 2002 Wiley‐Liss, Inc.