Concepts of immortalization in human mammary epithelial cells.

Abstract

Cellular immortality is a hallmark of neoplastic transformation, the detection of which in vitro may be only limited by providing stringent culture conditions for neoplastic cells. Unlike cultured rodent cells, spontaneously immortal human mammary epithelial cell lines cultured from presumably normal cells have rarely been identified. Only two reports described cell lines that arose in mammary tissue explants obtained from women with fibrocystic disease or intraductal hyperplasia (Briand et al. 1987; Soule et al. 1990). For clarity, and by definition, a normal human mammary epithelial cell (HMEC) population or clone that eventually senesces in culture is termed a “strain”, while a clone or population that has unlimited replicative potential is termed a “line”. The principles and players that confer unlimited in vitro replicative potential upon HMEC strains overlap partially with findings from cultured human diploid lineages, e.g., fibroblast-like cells and keratinocytes. Similarities between immortalized fibroblast-like cultures and HMECs include the functional repression of cell cycle- and DNA damage responsive-proteins p53, pRB, p16, and p21 (reviewed in Campisi et al. 1996; Garkavtsev et al. 1998). Nonetheless, human HMECs have unique phenotypes and require stringent culture conditions. This chapter will be limited to a discussion of human-derived mammary epithelial cells.