Three cell lines showing androgen-dependent, -independent, and -suppressed phenotypes, established from a single tumor of androgen-dependent Shionogi carcinoma 115.
We investigated the heterogeneity of cells in terms of androgen responsiveness within a single tumor mass of Shionogi carcinoma SC-115 showing androgen-dependent growth. After cloning of the tumor by the limiting dilution method in the presence of androgen, we isolated 40 clones at random. Twenty-two clones required androgen for growth (androgen-dependent phenotype), 16 did not (androgen-independent phenotype), and the remaining two clones showed growth inhibition when androgen was added (androgen-suppressed phenotype). In addition, 22 androgen-dependent clones showed heterogeneity in growth factor sensitivity in the absence of androgen. All clones were sensitive to both acidic and basic fibroblast growth factor (FGF), 7 of 22 clones were sensitive to epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha, and 2 of 22 clones were sensitive to TGF-beta. This preexisting heterogeneity may be partly responsible for the growth of androgen-dependent tumor under hormone-deprived circumstances. Three typical clones, SC2G, SC1G, and SC4A, were selected from androgen-dependent, -independent, and -suppressed phenotypic groups, respectively. These clones, as well as original solid tumors, were found to produce heparin-binding growth factors of heterogeneous elution positions. The molecular nature of these growth factors is not yet known. Neither anti-basic FGF antibody nor anti-EGF antibody inhibited the cell growth when added in cell culture, suggesting the factors were distinct from basic-FGF and EGF.
Yamaguchi
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kawamoto
K
K
Uchida
N
N
Uchida
K
K
Watanabe
S
S
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000276:immunology / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D013739:Testosterone / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D000906:Antibodies; D016211:Transforming Growth Factor alpha; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D013739:Testosterone; D004815:Epidermal Growth Factor