Translocation of lysophosphatidic acid phosphatase in response to gonadotropin-releasing hormone to the plasma membrane in ovarian cancer cell

Sun, Wen-Shu; Imai, Atsushi; Sugiyama, Michiyo; Furui, Tatsuro; Tamaya, Teruhiko; Saio, Masanao; Morris, Andrew J

doi:10.1016/j.ajog.2004.01.038

« Previous Next »American Journal of Obstetrics & Gynecology
Volume 191, Issue 1 , Pages 143-149, July 2004

Translocation of lysophosphatidic acid phosphatase in response to gonadotropin-releasing hormone to the plasma membrane in ovarian cancer cell☆

Department of Obstetrics and Gynecology^a and 2nd Department of Pathology,^b Gifu University School of Medicine, Gifu, Japan; Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC^c USA

Received 20 July 2003; received in revised form 31 December 2003; accepted 21 January 2004.

Abstract

Objective

Lysophosphatidic acid mediates proliferative and/or morphologic effects on multiple cell lineages, which include ovarian cancer cells. Lysophosphatidic acid hydrolysis limits the duration of lysophosphatidic acid's action. We examined hormonal translocation of lipid phosphate phosphatase type 3 to the plasma membrane in gonadotropin-releasing hormone–responsive ovarian cancers.

Study design

Ovarian cancers that were removed surgically and the ovarian cancer cell lines Caov-3 and SK-OV-3 were examined. Lipid phosphate phosphatase type 3 protein and activity in plasma membranes were assessed by immunohistochemical staining with lipid phosphate phosphatase type 3–specific antibodies and by the measurement of the conversion of exogenous [³H-oleoyl]lysophosphatidic acid to mono[³H-oleoyl]glycerol, respectively.

Results

In ovarian cancers that were removed surgically, the cell surface staining and activity measurements indicated that a portion of the enzyme was localized to the plasma membrane. In Caov-3 cells and SK-OV-3 cells, lipid phosphate phosphatase type 3 protein was present both in the cytoplasm and at the plasma membrane. Treatment of the cells with a gonadotropin-releasing hormone agonist buserelin produced a rapid and progressive translocation of lipid phosphate phosphatase type 3 protein to the plasma membrane, with a concomitant loss of cytoplasmic staining. The enzyme activity in plasma membrane was also increased when the cell lines were exposed to the gonadotropin-releasing hormone agonist in intact cells before the assay of the cell membranes.

Conclusion

These findings support the presence of lipid phosphate phosphatase type 3 in plasma membrane of ovarian cancers and provide for the ability of agonists (such as gonadotropin-releasing hormone) to induce the translocation of lipid phosphate phosphatase type 3 to plasma membrane in ovarian cancer cells.

Keywords: Phosphatase, Lysophosphatidic acid, Ovarian cancer, Gonadotropin-releasing hormone, Antiproliferative action