Aberrant energy metabolism in a variant epidermal growth factor receptor-negative fibroblastic cell line

Abstract

A variant 3T3 cell line has been isolated [l] lacking mitogenic response to epidermal growth factor [2,3]. This non-responder variant (NR-6) lacked epidermal growth factor (EGF) receptors, but retained the ability to respond to other mitogens, and displayed growth control in culture [ 11. NR-6 cells have been used as specificity controls in identification of the EGF receptor [4-61 on 3T3 cells and for studies on insertion of exogenous hormone receptors into receptornegative mutant cells [7]. We were interested in further character~ing this variant cell line, and examined whether the lack of EGF receptors is accompanied by other losses as well. Such studies may provide new insights into receptor genetics and the regulatory mechanisms involved in receptor biosynthesis. Here we report our preliminary findings on the energy metabo~sm characteristics of NR-6 cells. We find that compared with the parent 3T3 cells, the variant NR-6 cells are extremely deficient in cytochrome c oxidase, a key enzyme in the oxidative phosphorylation pathway, but this deficiency is compensated for by an exceptionally high rate of aerobic glycolysis. This aberrant energy metabolism does not appear to be associated with any transformed growth characteristics.