Oncogene expression cloning by retroviral transduction of adenovirus E1A-immortalized rat kidney RK3E cells: Transformation of a host with epithelialfeatures by c-MYC and the zinc finger protein GKLF

The function of several known oncogenes is restricted to specific host cell s in vitro, suggesting that new genes may be identified by using alternate hosts. RK3E cells exhibit characteristics of epithelia and are susceptible to transformation by the G protein RAS and the zinc finger protein GLI, Exp ression cloning identified the major transforming activities in squamous ce ll carcinoma cell lines as c-MYC and the zinc finger protein gut-enriched K ruppel-like factor (GKLF)/epithelial zinc finger. In oral squamous epitheli um, GKLF expression was detected in the upper, differentiating cell layers. In dysplastic epithelium, expression was prominently increased and was det ected diffusely throughout the entire epithelium, indicating that GKLF is m isexpressed in the basal compartment early during tumor progression. The re sults demonstrate transformation of epithelioid cells to be a sensitive and specific assay for oncogenes activated during tumorigenesis in vivo, and i dentify GKLF as an oncogene that may function as a regulator of proliferati on or differentiation in epithelia.