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

Mar 4, 2000The Journal of pathology

Oxytocin receptors in human uterine gland cancers: their presence and possible role

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Abstract

Oxytocin receptors (OTRs) were found in 82% of endometrial carcinomas studied.

The presence of OTRs was observed in a majority of human adenocarcinomas of the endometrium, with varied expression patterns based on tumor differentiation.
The OTR gene was detected in 78% of cases using reverse transcriptase-polymerase chain reaction (RT-PCR) and confirmed in selected cases by in situ hybridization (ISH).
Oxytocin treatment significantly inhibited the proliferation of a human endometrial carcinoma cell line without inducing toxicity or apoptosis.
The antiproliferative effect of oxytocin was negated by an inhibitor of protein kinase A, indicating a possible role for cAMP via PKA in mediating this effect.
These findings suggest that oxytocin and its receptors may play a role in regulating endometrial cells in both normal and cancerous conditions.

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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 and 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) procedures 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 positivity varying from diffuse to focal, according to tumour differentiation. The OTR 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 carcinoma 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 induced by OT treatment. The addition of an inhibitor of protein kinase A (PKA) to the culture medium abolished the antiproliferative effect of OT, suggesting that cAMP via PKA could be the intracellular mediator of the OT effect, 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 regulation of endometrial cells, not only in physiological conditions but also in a neoplastic context.

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

Abstract

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