Figure 1.

The test by transplantation. Transplantation in orthotopic or ectopic sites provides an experimental definition for normal (A), hyperplastic (B), precancer (C), or cancer (D) in mammary epithelial tissues. Fresh tissue fragments can be harvested from a “donor” mouse and transplanted into a “recipient” mouse, either in the orthotopic site—a gland-cleared mammary fat pad—where the tissue proximal to the lymph node in the inguinal mammary stroma is removed at 3 weeks of age; or, in an ectopic site such as subcutaneous stroma. (A) Normal tissue transplanted into the orthotopic site yields a normal gland outgrowth, but does not grow ectopically. After sequential “serial” transplant generations, the normal tissue will senesce, eventually resulting in no outgrowth. (B) Hyperplasias, in contrast, will not senesce after multiple serial transplant generations, but they still will not grow ectopically. (C) Precancer tissues are defined by immortal growth in serial transplantation, but are also defined by a progression to a lesion that will grow ectopically. (D) Cancer tissues, meanwhile, are consistently able to grow in either the orthotopic or ectopic site.