TGF‐α production correlates with tumorigenicity in clones of the SW613‐S human colon carcinoma cell line

Abstract
The c‐myc gene is amplified and the c‐Ki‐ras gene is mutated in the SW613‐S human colon carcinoma cell line. Two cell types with different levels of c‐myc amplification are present in the SW613‐S cell population and representative cell clones can be isolated. The clones with a high level of amplification and expression of the c‐myc gene are tumorigenic in nude mice whereas those with a low level are not. The tumorigenic clones secrete transforming growth factor a (TGF‐α) in the culture medium whereas the non‐tumorigenic clones do not produce any detectable amount. Accordingly the level of TGF‐α mRNA is higher and the transcription rate of the gene is increased in the tumorigenic clones. The acquisition of the tumorigenic pheno‐type by cells of non‐tumorigenic clones, following introduction of c‐myc gene copies by transfection, is accompanied by an increase in the steady‐state level of TGF‐α mRNA. These findings suggest a role for an elevated level of TGF‐α production in the tumorigenic phenotype of SW613‐S cells. The possibility that this role is indirect is discussed.