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

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Abstract
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.