Unlimited division potential of precancerous mouse mammary cells after spontaneous or carcinogen-induced transformation.

Serial transplantation of normal mouse mammary gland in young, isogenic hosts results in progressive loss of division potential, and the transplant line is eventually lost. This is interpreted as an expression of senescence at the cell and tissue level, and it inevitably occurs even though experimental conditions for growth are judged to be optimal. An indefinite extension of mammary growth span can be accomplished by transformation of these normal cells into precancerous cell types, which grow as a benign tissue but which may, however, occasionally undergo a second transformation into a malignant carcinoma. All precancerous tissues tested displayed unlimited growth potential, regardless of whether they occurred spontaneously, or were induced by oncogenic viruses or by administration of chemical carcinogens. Precancerous tissues of both ductal and lobuloalveolar morphology grew continuously. These results indicate that release from cell aging, as measured by the acquisition of unlimited growth potential, is associated with the precancerous state per se, and occurs as an early event in the transition from normal to malignant mammary cells.