Endocrine Abstracts (2002) 3 OC12

Ghrelin inhibits proliferation of breast cell lines acting via the growth hormone secretagogue receptor (GHS-R)

JP Taylor, BA Hughes, MC Sheppard, PM Stewart & AA Toogood

Department of Medicine, Division of Medical Sciences, The University of Birmingham, Birmingham, UK.

Ghrelin, the natural ligand for the GHS-R, modulates proliferation in cell lines derived from malignant breast tissue. It has been suggested that this action is independent of the GHS-R. We have previously demonstrated that MCF7 cells expressed ghrelin but not GHS-R mRNA and MDA-MB231 cells expressed GHS-R but not ghrelin mRNA. To determine whether ghrelin modulates proliferation in MCF7 and MDA-MB231 cells we performed proliferation assays treating with saline, 1 and 10nM ghrelin at 0, 24 and 48 hours. Cells were counted after 72 hours. To determine whether the GHS-R is implicated in the effects observed MCF7 cells were stably transfected with the GHS-R (MCF7/GHS-R). These were treated with the GHS-R antagonist BMS-265711 at time zero and counted after 72 hours.

Ghrelin decreased proliferation of MDA-MB231 cells after 72 hours at doses of 1nM (58% of control, P <0.01) and 10nM (63% of control, P <0.05). Ghrelin did not affect proliferation of receptor negative, wild-type (wt)MCF7 cells. Under normal culture conditions MCF7/GHS-R was significantly inhibited (66% vs. wtMCF7). BMS-265711 at concentrations of 1, 10 and 100nM did not affect proliferation of wtMCF7 cells, but increased proliferation of MCF7/GHS-R treated with 10nM (121% of control, P <0.05) and 100nM (122% of control, P <0.01).

These data demonstrate that ghrelin inhibits the proliferation of cell-lines derived from malignant breast tissue that express the GHS-R. Transfection of the GHS-R into cells that express ghrelin creates an autocrine loop that inhibits cell growth, a loop that can be disrupted by a GHS-R antagonist. These data indicate that ghrelin acts via the GHS-R to modulate cell proliferation.

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