DIFFERENTIAL TEMPORAL AND SPATIAL GENE-EXPRESSION OF FIBROBLAST GROWTH-FACTOR FAMILY MEMBERS DURING MOUSE MAMMARY-GLAND DEVELOPMENT

Mammary gland development is dependent upon local regulatory factors as well as systemic hormones to mediate gland morphogenesis and associated mesenchymal-epithelial interactions. FGF-3 (int-2) has been implicated as an oncogenic growth factor produced locally in mouse mammary tumor virus-induced mammary tumorigenesis. The observation that FGF-3 is not expressed during normal mammary development as well as the high degree of cellular proliferation and angiogenesis that accompany mammary gland growth suggest roles for other FGF family members in this process. In this study, we have examined expression of FGF family members at various stages of mouse mammary growth and tumorigenesis. FGF-1, FGF-2, FGF-4, and FGF-7 were expressed during the ductal stage of mammary development. The majority of FGF-1 gene expression was in the luminal epithelial cells, whereas FGF-2 expression was in the mammary stroma and possibly the myoepithelial cells. The presence of mammary epithelium induced th expression of both FGF-2 and FGF-7 in the stroma. FGF-1 and FGF-2 expression declined during pregnancy and dropped again during lactation, but quantitative analysis showed a much more dramatic decrease in FGF-2 expression. FGF-7 transcripts were also detected during pregnancy and lactation, but an alternate transcript size was observed at these stages. FGF-1, FGF-2, and FGF-7 transcripts were detected in mammary preneoplasias, tumors, and immortal cell lines, but at levels less than those seen during normal mammary growth. These results support the hypothesis that FGF family members play a role in local regulation of mammary development. The differential spatial and temporal pattern of FGF-1, FGF-2 and FGF-7 gene expression indicate that they each have unique functions in the gland.