Alkaline phosphatase activity and the regulation of growth in transformed mammalian cells

The relationship between alkaline phosphatase activity and cell growth has been studied in hamster cells transformed by different carcinogens. About 90% of normal hamster embryo cells were constitutively positive for alkaline phosphatase activity (AP + ). However, there were no AP + cells in cell lines transformed after treatment with the chemical carcinogens dimethylnitrosamine or 4‐nitro‐quinoline‐N‐oxide and 0.02% and 4% AP + cells in cell lines transformed by polyoma virus or Simian virus 40. The glucocorticoid hormone, prednisolone, induced alkaline phosphatase activity in 12% and 44% of the enzyme‐negative (AP − ) cells in cell lines transformed by polyoma or Simian virus 40, but this hormone did not induce alkaline phosphatase activity in AP − cells from cell lines transformed after treatment with the chemical carcinogens. Treatment of polyoma transformed AP − cells with the mutagen N‐methyl‐N′‐nitro‐N‐nitro‐soguanidine produced AP + cells, whereas no AP + cells were found after mutagen treatment of AP − cells from the chemically transformed cell lines. Studies on spontaneous segregation in the polyoma transformed cell line has shown that AP + cells segregated AP − cells both in vitro and in vivo, although no spontaneous segregation was observed from AP − to AP + cells. AP + cells, compared to AP − cells, showed a decrease in DNA synthesis, cell multiplication, the ability to form colonies in soft agar and tumorogenicity in animals. AP − cells induced for alkaline phosphatase activity by prednisolone, showed the same growth properties in vitro as uninduced AP − cells. The decreased cell growth found in AP + cells which were constitutive for alkaline phosphatase activity was therefore not found in the hormone induced AP − cells. The results indicate that constitutive alkaline phosphatase activity appears to be related to the regulation of cell growth and that AP − cells have a selective advantage over AP + cells.