Mammary tumour virus and casein gene transcription during mouse mammary development

Abstract

MORPHOGENESIS and differentiation of the murine mammary gland is dependent on the interaction of peptide and steroid hormones. These hormones cause mammary growth through proliferation of ductal and alveolar epithelial cells1,2 and differentiation of the gland for the production of the milk proteins, casein and α-lactalbumin2–4. Mammary development frequently increases the incidence and results in an earlier onset of mammary tumours5,6. The influence of mammary development upon tumorigenesis has been correlated with the appearance of mouse mammary tumour virus (MMTV) particles6–10. Importantly, the production of MMTV particles is dependent on alveolar differentiation and function7,11. Lactating mammary glands from BALB/c mice contained considerably lower levels of MMTV RNA than glands from C3H mice infected with the milk-transmitted virus MMTV-S (ref. 12). In this study we have examined the influence of the hormonal changes that occur during mammary development on MMTV and casein expression by molecular hybridisation with specific complementary DNA (cDNA) probes to MMTV 70S RNA and casein 15S mRNA. Hence, the relationship between MMTV expression and the expression of a normal differentiated mammary function—the production of casein mRNA—was determined. We have quantitated MMTV RNA and casein mRNA in developing mammary tissues from BALB/c and BALB/cfC3H mice that have a low and high incidence of mammary tumours respectively6,13. These studies demonstrate that the hormonal alterations occurring during mammary development enhanced MMTV RNA expression to a greater extent in the high than the low tumour-incidence strain, whereas similar changes in the level of casein mRNA were observed in both strains during mammary development.