Species-specificity of estradiol regulated growth factors in breast cancer

Recent evidence indicates that autocrine/paracrine mechanisms may mediate the mitogenic effect of estradiol (E₂) both in human and experimental breast cancer. However, the species-specificity of E₂-regulated growth factors with regard to their biologic action has not been evaluated. To test this issue, we examined, in the soft agar clonogenic assay, the colony-stimulating activity in human breast cancers of conditioned media obtained from rat mammary carcinomas exposed to E₂ (rat E₂-CM). Of 22 primary human breast cancers plated in soft agar in the absence of serum, 18 (82%) successfully grew with a mean colony number of 62.4 ± 9.8 (S.E.M.) (range 14-193). Rat E₂-CM significantly stimulated colony formation in 10 18 (56%) human breast cancers to 155 ± 11% (S.E.M.) of control. E₂ administration (10^-9 M) in these tumors had a virtually identical overall effect (154 ± 13% of control colony number). In the remaining eight tumors (44%), neither rat E₂-CM nor E₂ had, in general, a significant colony-stimulating effect. The growth-promoting action of rat E₂-CM and E₂ was not influenced by the hormone receptor status of the tumor. These results suggest that E₂-regulated growth factors may not be species-specific, at least with regard to their colony-stimulating effects in soft agar.