Role of the EGF-Related Growth Factor Cripto in Murine Mammary Tumorigenesis

摘要

We are investigating growth factor signaling in the mammary gland through theanalysis of Cripto, a gene that is distantly related to epidermal growth factor (EGF). Previous studies have suggested that Cripto may play an autocrine or paracrine role in human breast, colorectal, gastric, and pancreatic carcinomas. To assess whether Cripto plays a role in normal breast development and whether it has a causal role in tumorigenesis, we have generated retroviruses and transgene constructs to examine the consequences of ectopic expression in cell culture and in transgenic mIce. To analyze receptor binding by CRIPTO protein and to initiate the molecular cloning of the CRIPTO receptor(s), we have generated histochemical affinity reagents to assay binding to cell-surface receptors. Using these reagents, we have demonstrated quantitative receptor binding of CRIPTO to mammary cell lines, and have observed a highly localized distribution of CRIPTO binding sites to tissue sections during early mouse development. These results demonstrate the existence of high-affinity CRIPTO receptors and represent the groundwork for their molecular identification.