DETECTION OF AMPHIREGULIN AND CRIPTO-1 IN MAMMARY-TUMORS FROM TRANSGENIC MICE

Epidermal growth factor family members are widely expressed in human b reast cancer and are thought to play an important dual role in mammary gland development and tumorigenesis. Overexpression of two relatively new members of this family, amphiregulin (AR) and Cripto-1 (CR-1), ha s been previously shown to transform immortalized human and mouse mamm ary epithelial cells. Here, we extend these results and address the dy sregulated expression of AR and CR-1 in many types of transgenic neopl astic mouse mammary tissues. Transgenic mouse strains overexpressing t he oncogenes transforming growth factor-alpha, neu, int-3, polyoma vir us middle T antigen, and simian virus 40 large T antigen have been pre viously shown to develop spontaneous mammary neoplasia. These models w ere each examined for mammary-tumor expression of AR and CR-1 by rever se transcription-polymerase chain reaction, western blot, and immunocy tochemical analyses. Mammary tumors from each source expressed AR and CR-1. Western blot analysis revealed that, in all mammary tumors, AR a nd CR-1 protein species were processed differently than in virgin and lactating mouse mammary tissue. In addition, immunohistochemical detec tion of AR and CR-I in tumor tissue revealed different patterns of gro wth-factor localization in different types of transgenic mouse mammary -derived tumors. These findings are consistent with the possibility of widespread roles for AR and CR-1 in the promotion and/or progression stages of mouse mammary tumorigenesis. (C) 1996 Wiley-Liss, Inc.