Oxytocin receptors in human adenocarcinomas of the endometrium: presence and biological significance

Oxytocin receptors (OTRs) are expressed in endometrial cells and oxytocin ( OT) participates in endometrial functions. In cancers derived from other OT target tissues, such as breast and neural tissues, the expression of OTRs and the antiproliferative effect of OT on cancer cells has been previously observed, This study was therefore designed to search for OTR expression an d the OT effect in endometrial carcinomas. To demonstrate the presence and the location of OTRs and OTR mRNA immunocytochemical, reverse transcriptase -polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) procedu res were employed in a series of human adenocarcinomas of the endometrium, Using an anti-OTR monoclonal antibody (IF3), OTRs were demonstrated in the large majority of endometrial carcinomas (82%), with a pattern of positivit y varying from diffuse to focal, according to tumour differentiation, The O TR gene was demonstrated in 78% of the cases by RT-PCR and its presence was confirmed in selected cases by ISH. Moreover, in a human endometrial carci noma cell line (COLO 684) OTR was demonstrated by immunofluorescence and RT -PCR and it was observed that OT treatment (10(-11)-10(-7) M) significantly inhibited cell proliferation. Neither toxic effects nor apoptosis were ind uced by OT treatment, The addition of an inhibitor of protein kinase A (PKA ) to the culture medium abolished the antiproliferative effect of OT, sugge sting that cAMP via PKA could be the intracellular mediator of the OT effec t, as previously observed in breast and neural tumours, In conclusion, this study presents evidence of OTR expression in human endometrial carcinomas and of an OT antiproliferative effect on human endometrial cancer cells in vitro. It is further suggested that OT and OTR may be involved in the regul ation of endometrial cells, not only in physiological conditions but also i n a neoplastic context. Copyright (C) 2000 John Wiley & Sons, Ltd.