DIFFERENTIAL GROWTH-FACTOR RESPONSES OF EPITHELIAL-CELL CULTURES DERIVED FROM NORMAL HUMAN PROSTATE, BENIGN PROSTATIC HYPERPLASIA, AND PRIMARY PROSTATE CARCINOMA

Because of a lack of information of the optimum nutritional requiremen ts, epithelial cells derived from normal human prostate and prostate t umors have been difficult to propagate in vitro, which hinders researc h in prostate carcinogenesis. In an effort to establish optimum nutrit ional conditions and differences in growth characteristics of normal h uman prostate (NP), benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCA), we have compared the effects of several growth factor s on cell proliferation and elucidated growth properties of low passag e epithelial cells derived from NP, BPH, and PCA of an African-America n patient. Primary and low passage cultures were propagated in serum-f ree keratinocyte basal medium (KBM) supplemented with insulin (5 mu g/ ml), hydrocortisone (0.5 mu g/ml), epidermal growth factor (EGF, 10 ng /ml), bovine pituitary extract (BPE; 50 mu g/ml), cholera toxin (10 ng /ml), and antibiotics. Almost all NP, BPH, and PCA cells were positive for cytokeratins and prostate-specific antigen (PSA). The NP, BPH, an d PCA cells were essentially diploid and lacked mutations in c-K-ras a nd c-Ha-ras oncogenes, and p53 tumor suppressor gene. However, they ex hibited progressively accelerating growth parameters. The population d oubling times of NP, BPH and PCA were 51 hr, 37 hr, and 29 hr, respect ively; their saturation densities were 2.9 x 10(4)/cm(2), 3.3 x 10(4)/ cm(2), and 7.2 x 10(4)/cm(2), respectively. The NP and BPH cells requi red all of the growth factors in the medium, as deletion of any one of the above factors strongly inhibited their growth. The PCA cells, how ever, were independent of EGF and hydrocortisone. PC-3, an established human prostate cancer cell line, was independent of the growth factor s tested. Fetal bovine serum (FBS) inhibited the growth of NP, BPH and PCA cells. In contrast, FBS stimulated the growth of the PC-3 cells i n a concentration-dependent manner. These results indicate that in the absence of any apparent karyotype alterations and mutations in c-K-ra s, c-Ha-ras and p53 genes, epithelial cells derived from NP, BPH, and PCA exhibit significant differences in their growth properties and res ponses to growth factors. These variations may represent early changes involved in prostate cancer, while gene mutations and cytogenetic alt erations occur in advanced and/or metastatic tumors. (C) 1996 Wiley-Li ss, Inc.