Premium
Oxytocin inhibits the proliferation of MDA‐MB231 human breast‐cancer cells via cyclic adenosine monophosphate and protein kinase A
Author(s) -
Cassoni Paola,
Sapino Anna,
Fortunati Nicoletta,
Munaron Luca,
Chini Bice,
Bussolati Gianni
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970717)72:2<340::aid-ijc23>3.0.co;2-i
Subject(s) - endocrinology , medicine , intracellular , inositol , adenosine , cyclic adenosine monophosphate , receptor , cell growth , second messenger system , protein kinase a , tyrosine kinase , biology , oxytocin , inositol phosphate , cancer cell , phosphorylation , cancer , biochemistry
Oxytocin (OT) inhibits the proliferation of breast‐cancer cells in vitro via a specific G‐coupled receptor. To elucidate the intracellular mechanism involved in this biological effect, different G‐coupled receptor mediators have been investigated in untreated and OT‐treated MDA‐MB231 breast‐carcinoma cells. In these cells, after OT treatment, a significant cAMP increase was observed using a radioimmunoassay procedure, whereas the Ca 2+ (determined with the fluorescent probe fura‐2) and the inositol phosphate (determined after cell labeling with myo(2‐ 3 H)‐inositol) concentrations were not modified, contrary to what has been observed in myometrial and myo‐epithelial cells. The PKA inhibitor PKI (6‐22) amide reverted the effect of OT, indicating that the anti‐proliferative effect of the peptide is strictly related to the cAMP–PKA pathway. OT treatment did not modify tyrosine phosphorylation either. Our results indicate that in breast epithelial cells devoid of contractile activity, cAMP is the intracellular mediator of OT action, whereas the Ca 2+ ‐phosphoinositide system is not involved. Int. J. Cancer 72:340–344, 1997. © 1997 Wiley‐Liss, Inc.