Concerning the Necessary Coupling of Development to Proliferation of Mouse Mammary Epithelial Cells

The epithelial cells from mammary glands of mature virgin mice synthesize increasing levels of casein and α-lactalbumin when cultured in the presence of insulin, hydrocortisone, and prolactin. When DNA synthesis is blocked in these cultures by the addition of cytosine arabinoside or 5-fluorodeoxyuridine, augmented milk-protein production does not occur. The effects of cytosine arabinoside are prevented by simultaneous addition of deoxycytidine. Neither cytosine arabinoside nor 5-fluorodeoxyuridine have a postmitotic inhibitory effect on casein or α-lactalbumin synthesis. The insulin-induced increase in the combined activities of the intracellular proteins glucose-6-phosphate dehydrogenase and gluconate-6-phosphate dehydrogenase is not affected by either inhibitor. Such a necessary coupling of secretory protein production to DNA synthesis or mitosis or both no longer exists in explants from midpregnant mice. Most of the epithelial cells of this tissue have already undergone their "critical mitosis" in vivo.