The potential involvement of Epidermal Growth Factor (EGF), Transforming Growth Factor-alpha, Amphiregulin (AR), Epidermal Growth Factor-Receptor (EGF-R), and c-erbB-2 in the initiation and progression of human ovarian epithelial cancer was investigated by comparison of the mRNA and protein level of these genes in carcinoma cell lines and normal ovarian surface epithelian (OSE) cells. All 17 ovarian carcinoma cell lines which were examined expressed EGF-R (Kd equals 0.21 to 5.3 nM) and 16 cell lines, in addition, concomitantly secreted TGF-alpha (16 to 197 pg/ml). The growth of 8 carcinoma lines was stimulated in a dose-dependent manner when grown in the presence of exogenous TGF-alpha (30 to 88 percent). Growth in 4 of 5 of the cell lines capable of serum-free propagation was inhibited (28 to 56 percent) when cultured in medium containing a TGF-alpha neutralizing monoclonal antibody. Concentrations of AR ranging from 1-5 nM stimulated the growth of 3 OSE samples (20 to 50 percent) and 4 of 6 carcinoma cell lines (28 to 210 percent). Differential immunohistochemical detection of AR and cripto was documented in normal human colon and colorectal tumors. Whereas normal colon did not express cripto, 86 percent of the tubulo adenomas, but only 43 percent of the tubular adenomas were positive for cripto expression. AR expression appeared to be associated with both normal and malignant colonic epithelial cells that were more differentiated. AR localizes in both nucleus, and cytoplasm by immunohistochemistry of ovarian carcinoma and normal ovarian surface epithelial cells, and functions in an autocrine manner in a colon carcinoma cell line.
