Infection with a transforming growth factor α anti-sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line

Transforming growth factor α (TGFα) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGFα. GEO cells, from a human colon carcinoma cell line that expresses TGFα and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGFα cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein 1 promoter. Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGFα AS cells). A 50 to 70% inhibition in the production of secreted and cell-associated TGFα protein was observed in GEO TGFα AS cells that had been maintained in CdCl₂-supplemented medium. Moreover, a growth inhibition of 70% and 50% was observed in CdCl₂-treated GEO TGFα AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively. In contrast, CdCl₂ treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGFα may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor.