Retroviral expression of transforming growth factor-alpha does not transform fibroblasts or keratinocytes

Abstract

Transforming growth factor α (TGFα) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells. To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGFα. Infection of NIH/3T3 cells with the TGFα retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGFα, but failed to induce morphologic transformation. Similarly, the TGFα retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts. We also investigated the effect of TGFα expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation. We show that exogenously added TGFα is an extremely potent mitogen for BALB/MK cells. However, retroviral expression of TGFα in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGFα) for cell growth. These results suggest that overexpression of TGFα does not, by itself, transform rodent fibroblasts or keratinocytes. © 1990.