Response to and expression of amphiregulin by ovarian carcinoma and normal ovarian surface epithelial cells: nuclear localization of endogenous amphiregulin.

Amphiregulin (AR) is a polypeptide growth regulator which has sequence homology to the epidermal growth factor-related family of ligands and contains putative nuclear targeting sequences. Human ovarian carcinoma cell lines and their normal counterparts, ovarian surface epithelial cells (OSEs), were assessed for their ability to respond to and express AR. Addition of exogenous AR (8-200 pM) inhibited the growth of 2 of 3 OSE specimens and 3 of the 6 carcinoma cell lines indicating that AR has the potential to inhibit the growth of normal cells, in addition to carcinoma cells. In contrast, concentrations of AR ranging from 1-5 nM stimulated the growth of all 3 of the OSEs and 4 of the 6 carcinoma cell lines. Immunocytochemical staining of the cells using antipeptide antibodies directed against residues 8-26 of AR indicated that all cells expressed AR and that the staining was localized to the nucleus. The nuclear staining of AR was concentrated in the nucleolus of the carcinoma cells, whereas the staining was diffuse in the nucleus of the OSEs. These results suggest that AR may play a growth regulatory role in the nucleus of cells and this role may be different in normal and malignant epithelial cells.