TRANSFORMING GROWTH-FACTOR-ALPHA LOCALIZATION AND ROLE IN SURFACE EPITHELIUM OF NORMAL HUMAN OVARIES AND IN OVARIAN-CARCINOMA CELLS

Transforming growth factor alpha (TGFalpha) has been localized by immu nohistochemistry in the ovarian surface epithelial (OSE) cells of sect ions from normal human ovaries and in epithelial cells of surface cryp ts. An ovarian cancer cell line (HEY) derived from the surface epithel ium of a human ovary also exhibited intense staining for the TGFalpha peptide. Using Northern analysis, HEY cells were shown to express a 4. 5-kb transcript of TGFalpha, indicating that the TGFalpha peptide was synthesized by these cells and not taken up from the serum in the cult ure medium and sequestered by the cells. This was confirmed using a ra dioimmunoassay, which showed that HEY cells in culture secrete TGFalph a peptide, both as a soluble (0.12 +/- 0.02 ng/mg protein) and as a me mbrane-anchored (0.06 +/- 0.006 ng/mg protein) form. In both normal OS E cells and HEY cells, TGFalpha acted as a growth promoter: TGFalpha s ignificantly stimulated [H-3]thymidine incorporation into DNA of both primary cultures of normal OSE cells (2.7-fold) and of HEY cells (2-fo ld). This study provides the first demonstration of TGFalpha immunosta ining in normal surface epithelial cells and in HEY cells, and suggest s that TGFalpha, localized in normal and transformed OSE, is an autocr ine growth promoter for these cells. (C) 1994 Academic Press, Inc.