DOWN-MODULATION OF EPIDERMAL GROWTH-FACTOR RECEPTOR ACCOMPANIES TNF-INDUCED DIFFERENTIATION OF THE DIFI HUMAN ADENOCARCINOMA CELL-LINE TOWARD A GOBLET-LIKE PHENOTYPE

Although the biologic response modifier tumor necrosis factor-alpha (T NF) is a known differentiation inducer in hematopoietic cells, its rol e in differentiation of other tissue types has yet to be elucidated. I n the studies presented here, TNF treatment of the human rectal adenoc arcinoma cell line, DiFi, elicits characteristics of early stage diffe rentiating, mucin-producing colonocytes. Not only are TNF-treated DiFi cells growth-inhibited by TNF, but they also display a unique morphol ogy. Additionally, TNF treatment of DiFi cells enhances > fivefold the expression of high molecular weight mucin glycoproteins, as measured by [I-125]-wheat germ agglutinin (WGA) binding and the human milk fat globule-I (HMFG-1) anti-MUC1 antibody reactivity. The induction of the se differentiation characteristics correlates with novel alterations i n epidermal growth factor receptor (EGF-R). Following 5-day TNF treatm ent of DiFi cultures, EGF receptor levels, kinase autophosphorylation activity, and receptor tyrosine phosphorylation are reduced by > fourf old. The establishment of a model system in which goblet-like cell cha racteristics and alterations in a growth factor receptor can be induce d in vitro may be potentially useful in studying the underlying mechan isms of colonic epithelial cell proliferation and differentiation. (C) 1993 Wiley-Liss, Inc.