Morphological and functional properties of TM preneoplastic mammary outgrowths

The TM series of preneoplastic mammary outgrowth lines was derived from the transplantation of the FSK mammary cell lines into the cleared mammary fat pads of syngeneic female BALB/c mice. The tumor-producing capabilities of the 6 TM outgrowth lines varied from high (TM2, -4, -6) to low (TM9, -10) to nil (TM3). Outgrowth lines 2, 4, and 6 each segregated into sublines of high and low tumor potential. The majority of the outgrowth lines exhibited a moderate to dense alveolar hyperplasia typical of mouse mammary hyperplasias. The exceptions to this picture were lines TM2H and TM10 which exhibited a unique ductular morphology. The ductular morphology was not correlated with tumor potential of the outgrowth lines but was correlated with the expression of K6 and K14 keratins in luminal epithelial cells. In an examination of the growth and hormonal responsiveness properties of the TM outgrowth lines, the TM3 line stands as distinct from the other lines and from any other lines previously characterized in BALB/c mice. The TM3 line grew very slowly and failed to fill the fat pad by 12 months of age. At 12 months of age, the alveolar hyperplasia had regressed so that only bare ducts were present. The TM3 outgrowth was ovarian hormone dependent for growth and alveolar differentiation. TM3 outgrowth represents a minimally deviated mammary hyperplasia which has acquired the immortal phenotype but not the other phenotypic characteristics of mammary preneoplasias. This outgrowth line will be useful for examining the essential molecular changes important for the preneoplastic state, some of which are reported in an accompanying paper (D. Medina et al., Cancer Res., 53: 668-674, 1993).