Effects of growth factors on an intestinal epithelial cell line: Transforming growth factor β inhibits proliferation and stimulates differentiation

The effects of epidermal growth factor transforming growth factor β (TGFβ) and other growth factors on the proliferation and differentiation of a cell line derived from rat intestinal crypt epithelium (IEC-6) were defined. Incorporation of [³H]-thymidine was stimulated 1.4-2.4 fold by insulin, insulin like growth factor (IGF), platelet derived growth factor (PDGF), epidermal growth factor (EGF) and 2% fetal calf serum (FCS) respectively. Additive stimulation was observed when FCS was supplemented by insulin, IGF-I or PDGF but not EGF. Incorporation of [³H]-thymidine by IEC-6 was strongly inhibited by TGFβ with greater than 80% inhibition of incorporation at concentration ≅ 2.0 pM. IEC-6 cells bound 4.1±0.15×10⁴ molecules TGFβ/cell and appeared to have only a single class of high affinity receptors (Kd ≅ 0.5 pM). TGFβ inhibition was unaffected by the presence of insulin or IGF-I suggesting it inhibits proliferation at a step subsequent to that at which these growth factors stimulate [³H]-thymidine incorporation. TGFβ also reduced the stimulation induced by FCS by 65%. In contrast EGF reduced TGFβ inhibition by 60%. IEC-6 cells demonstrated the appearance of sucrase activity after > 18 hours treatment with TGFβ. These findings suggest that TGFβ may inhibit proliferative activity and promote the development of differentiated function in intestinal epithelial cells.