OSTEOPONTIN EXPRESSION IN MAMMARY-GLAND DEVELOPMENT AND TUMORIGENESIS

Osteopontin (OPN) is a secreted phosphoprotein that binds to cells via an Arg-Gly-Asp sequence and to mineralized surfaces, The protein can mediate cell adhesion and is strongly implicated in transformation and tumorigenesis, We have examined the expression pattern of OPN in mous e mammary glands at different stages of postnatal development, Whereas OPN is expressed at low-to-moderate levels in mammary glands from vir gin and pregnant mice, the levels of OPN mRNA are extremely high in th e lactating gland, consistent with the presence of the protein in milk , Expression is highest at 2 days of lactation and declines thereafter , but it remains high through involution, OPN expression is restricted to small nests or groups of cells at 9 days of involution. These resu lts suggest that OPN may play a specific role in the process of involu tion that may be distinct from its role during lactation. In mammary t umors arising spontaneously in transgenic mice expressing the oncogene s c-myc and/or v-Ha-ras under the control of the mouse mammary tumor v irus promoter, the level of OPN expression is increased dramatically o ver that in the normal gland in these same animals, Numerous cells exp ressing OPN mRNA are widespread throughout the tumors, OPN protein is detectable by Western blotting in extracts from the mammary gland at 2 days of lactation and from the tumors, but not in mammary glands at o ther stages of development, We hypothesize that OPN is exported from m ost tissues and that the protein is only detectable in tissues elabora ting fluids, such as the lactating mammary gland, or in pathological s ituations when expression of OPN is abnormally high, such as in tumors .