Transforming growth factor alpha localization and role in surface epithelium of normal human ovaries and in ovarian carcinoma cells.

Transforming growth factor alpha (TGF alpha) has been localized by immunohistochemistry in the ovarian surface epithelial (OSE) cells of sections from normal human ovaries and in epithelial cells of surface crypts. An ovarian cancer cell line (HEY) derived from the surface epithelium of a human ovary also exhibited intense staining for the TGF alpha peptide. Using Northern analysis, HEY cells were shown to express a 4.5-kb transcript of TGF alpha, indicating that the TGF alpha peptide was synthesized by these cells and not taken up from the serum in the culture medium and sequestered by the cells. This was confirmed using a radioimmunoassay, which showed that HEY cells in culture secrete TGF alpha peptide, both as a soluble (0.12 +/- 0.02 ng/mg protein) and as a membrane-anchored (0.06 +/- 0.006 ng/mg protein) form. In both normal OSE cells and HEY cells, TGF alpha acted as a growth promoter: TGF alpha significantly stimulated [3H]thymidine incorporation into DNA of both primary cultures of normal OSE cells (2.7-fold) and of HEY cells (2-fold). This study provides the first demonstration of TGF alpha immunostaining in normal surface epithelial cells and in HEY cells, and suggests that TGF alpha, localized in normal and transformed OSE, is an autocrine growth promoter for these cells.