Hepatocyte growth factor disrupts cell contact and stimulates an increase in type 3 inositol triphosphate receptor expression, intracellular calcium levels, and apoptosis of rat ovarian surface epithelial cells.

The present studies revealed that hepatocyte growth factor (HGF) disrupts cell contact, increases both type 3 IP3 receptor and intracellular calcium ([Ca2+]i) levels and induces apoptosis of rat ovarian surface epithelial cells (ROSE-179 cells). Type 3 IP3 receptor was only increased in cells that lost cell contact. Disrupting cell contact by depleting extracellular calcium (Ca2+) also resulted in an increase in [Ca2+]i levels and an increase in apoptosis. These responses were prevented by the addition of 0.7 mM Ca2+. Actinomycin D and cycloheximide prevented apoptosis that resulted from Ca2+ removal. In situ hybridization studies revealed that type 3 IP3 receptor was expressed at relatively low levels by ROSE-179 cells cultured with Ca2+ but at high levels in the absence of Ca2+. ROSE-179 cells cultured in Ca2+-free medium with type 3 IP3 receptor antisense oligonucleotide lost cell contact but did not show an increase in either type 3 IP3 receptor protein, [Ca2+]i, or apoptosis. The nonsense oligonucleotide did not alter these responses to Ca2+ removal. Thus, the disruption of cell contact by either HGF or Ca2+ depletion increases the expression of type 3 IP3 receptor, which causes an increase in [Ca2+]i and the apoptotic death of ROSE-179 cells.