TGF-alpha production correlates with tumorigenicity in clones of the SW613-S human colon carcinoma cell line.

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 alpha (TGF-alpha) in the culture medium whereas the non-tumorigenic clones do not produce any detectable amount. Accordingly the level of TGF-alpha mRNA is higher and the transcription rate of the gene is increased in the tumorigenic clones. The acquisition of the tumorigenic phenotype 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-alpha mRNA. These findings suggest a role for an elevated level of TGF-alpha production in the tumorigenic phenotype of SW613-S cells. The possibility that this role is indirect is discussed.