Hormonal Influences on the Expression of Casein Messenger RNA during Mouse Mammary Tumorigenesis¹

The expression of a differentiated mammary gland function, the production of casein messenger RNA (mRNA), was examined in preneoplastic outgrowth lines of BALB/c hyperplastic alveolar nodules (HAN) and a ductal hyperplasia (DH) as well as tumors that arose from the outgrowth lines. HAN and DH were induced in virgin BALB/c mice by hormonal stimulation and/or treatment with 7,12-dimethylbenz(a)anthracene. Outgrowth lines were established by serial transplantation of the HAN and DH. Casein 15S mRNA was quantitated in total cellular RNA by molecular hybridization with a labeled complementary DNA probe synthesized in vitro from purified mouse casein 15S mRNA. The level of casein 15S mRNA observed in BALB/c outgrowth lines and tumors ranged from 0.01% to less than 0.0005% of total cellular RNA. In comparison, about 0.05% casein mRNA was found in midpregnant BALB/c mammary glands. Virgin BALB/c mice bearing transplanted outgrowth lines or tumors were treated with prolactin (500 µg/day) and/or dexamethasone (100 µg/day) for 5 days to test the effect of these lactogenic hormones on the level of casein 15S mRNA. Significant increases in the level of casein 15S mRNA were observed with the combined hormone treatment in three of five HAN outgrowth lines, whereas the same hormone treatments did not significantly increase casein mRNA levels in the DH outgrowth line or any tumors derived from HAN or DH outgrowth lines. Therefore, the expression of a differentiated mammary gland function is hormonally responsive in BALB/c preneoplastic HAN outgrowth lines but not mammary tumors.