Expression of immunoreactive leptin and its receptor in epithelial ovarian cancer

Kim, Young Jae; Cho, Baik Seol; Cho, Sam Hyun; Kim, Kyung Tai; Park, Moon Il

Abstract

OBJECTIVE
Leptin, a secreted protein of the Ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic breast cancer cells. However, a potential role of leptin as an endocrine regulator is unknown in ovarian cancer. In the present study, we investigated the expression of leptin and its receptors in various histologic types of ovarian cancer and immortalized ovarian cancer cell lines to find out potential effect of leptin on the cell growth and activation of ovarian cancer cell line.
METHODS
The ovarian cancer tissues, serous (n=18), mucinous (n=15), clear cell (n=12) and endometrioid type (n=14), were used for immuno-histochemical staining for leptin (Ob) and leptin-receptors (Ob -R). Ovrian cancer cell lines (non-mucinous: SNU-8, OVCAR-3, and SKOV-3) and mucinous: MUC) were used for RT-PCR, Western blot analysis, and [H3] thymidine incorporation assay for the cell growth and activation of mitogen-activated protein kinase.
RESULTS
Both long (Ob-Rb) and short (Ob-Rt) isoforms of leptin receptors are expressed in non-mucinous type of ovarian cancer tissues (serous, clear cell carcinoma and endometrioid cell carcinoma) and in non-mucinous ovarian cancer cell lines (SNU-8, OVCAR-3 and SKOV-3 cells). However, leptin and its receptors are not found in mucinous cancer cells and mucinous cancer cell line (MUC). In immunohistochemical staining, the immunreactive leptin is expressed on the nuclei of the stratified cuboidal-to-columnar epithelial cells whereas its receptor was sparsely expressed on the innermost epithelial cell clusters and cytoplasm in non-mucinous tumor. However, there are no immunoreactive leptin and its receptor expressions in the mucinous tumor. In addition, treatment with leptin resulted in the growth stimulation of ovarian cancer cell line, an activation of ERK 1/2 and inhibition of constitutive phosphorylation of p38 Mitogen-activated protein kinase (MAPK).
CONCLUSION
Taken together, our data demonstrates preliminary that the expression of leptin and its receptor is different according to the cell types of the ovarian cancer. Also it canbe thought that leptin immunolocalized on the nuclei in non-mucinous type but not in mucinous possibly acts as a nuclear transcription factor. Further studies are necessary to validate whether leptin may be a potential regulator for ovarian cancer.