Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation

• Published in: Cell Vol. 46; no. 2; p. 301
• Main Authors: Rosenthal, A, Lindquist, P B, Bringman, T S, Goeddel, D V, Derynck, R
• Format: Journal Article
• Language: English
• Published: United States 18-07-1986
• Subjects: Animals; Cell Adhesion; Cell Transformation, Neoplastic - metabolism; DNA - metabolism; Female; Fibroblasts - metabolism; Growth Substances - physiology; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins - physiology; Peptides - metabolism; Peptides - physiology; Phenotype; Rats; Transforming Growth Factors
• ISSN: 0092-8674
• DOI: 10.1016/0092-8674(86)90747-6

Acquisition of the ability to produce and respond to a growth factor may result in increased cellular proliferation and could lead to malignant transformation. The fact that a large variety of tumor cells secrete transforming growth factor-alpha (TGF-alpha) suggests involvement of TGF-alpha in cellular transformation and provides supporting evidence for the autocrine stimulation model. In order to determine directly the role of TGF-alpha in tumorigenicity, we introduced a human TGF-alpha cDNA expression vector into established nontransformed Fischer rat fibroblast (Rat-1) cells. Synthesis and secretion of human TGF-alpha by these cells results in the loss of anchorage-dependent growth and induces tumor formation in nude mice. Anti-human TGF-alpha monoclonal antibodies prevent TGF-alpha expressing Rat-1 cells from forming colonies in soft agar.