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 ANA (mANA), was exam med 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. Out growth lines were established by serial transplantation of the HAN and DH. Casein 155 mRNA was quantitated in total cellular RNA by molecular hybridization with a labeled comple mentary 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 mam mary glands. Virgin BALB/c mice bearing transplanted out growth lines or tumors were treated with prolactin (500 @g/ day) and/or dexamethasone (100 ag/day) for 5 days to test the effect of these lactogenic hormones on the level of casein 155 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 mANA levels in the OH outgrowth line or any tumors derived from HAN or OH 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.