Effects of Growth Factors and Hormones on Growth and Morphological Differentiation of Human Breast Epithelial Cells within Collagen Gel in Serum‐free Medium

When human epithelial cells that had grown out from either carcinoma or histologically non‐malignant breast tissues were seeded within type I collagen gels in serum‐free medium, they successively grew and protruded many radial duct‐like extensions with lumina. Separate deletion of each of the supplements from the medium showed that growth as well as morphological differentiation of carcinoma‐derived cells were prevented in the absence of epidermal growth factor (EGF) or hydrocortisone. Removal of insulin or ethanolamine plus phosphoethanolamine caused a significant inhibition of cell growth without interfering with the morphological differentiation. Contrary to the case with carcinoma‐derived cells, both growth and morphological differentiation of epithelial cells derived from non‐malignant breast tissues were prevented when EGF, hydrocortisone or insulin was absent. Removal of each of the other supplements (except for transferrin), including ethanolamine plus phosphoethanolamine, prolactin, or prostaglandin, caused a significant inhibition of cell growth with no apparent inhibition of morphological differentiation. The present results suggest that human epithelial cells derived from either carcinoma or histologically non‐malignant breast tissues strongly depend on the presence of EGF and hydrocortisone and there is a decreased dependence on insulin in carcinoma‐derived cells with respect to their growth and morphological differentiation during culture within collagen gels.