Robert W. Holley

Activity of a kidney epithelial cell growth inhibitor on lung and mammary cells

A kidney epithelial cell growth inhibitor, isolated from BSC-1 cell-conditioned medium, has been found to be active on certain lung and mammary gland cell lines in culture. The most responsive cell observed thus far is the CCL64 mink lung cell line. With CCL64 cells, 60% inhibition of [3H]thymidine incorporation is observed at a 0.1 nanogram/ml concentration of the growth inhibitor, and approximately 95% inhibition at 1 nanogram/ml. A human mammary tumor cell line, Hs578T, shows 75% inhibition of [3H]thymidine incorporation, in cell culture. Preliminary studies indicate that injection of the kidney epithelial cell growth inhibitor in vivo into human mammary carcinomas growing in nude mice inhibits [3H]thymidine incorporation in the tumors.

Serum requirements for survival of 3T3 and SV3T3 fibroblasts

Abstract A serum factor that is labile to the action of pepsin is required for survival of 3T3 and SV3T3 cells. This ‘survival’ factor is distinct from growth-promoting factors in serum. Some properties of the factor are described.

Factors influencing the growth of alveolar type II epithelial cells isolated from rat lungs

Abstract Primary cultures of isolated alveolar type II cells have been established. Under appropriate conditions, these epithelial cells can be subcultured at least nine times. Using standard assay procedures, effects of growth factors or inhibitors can be studied. The alveolar type II cells show a marked response to both serum and growth factors in tissue culture. Either epidermal growth factor (EGF) or human urine gives an increase in thymidine incorporation (2-fold and 10-fold, respectively). The growth factor(s) in urine appears to be different from urogastrone (human EGF). The response to urine is several-fold greater than the response to a saturating concentration of mouse EGF alone. Mouse EGF added to urine does not increase the activity of urine. The period during which the alveolar type II cells respond to the growth factor(s) in urine is limited to early passages of the cells. Alveolar type II epithelial cells produce growth inhibitors in culture. Inhibitors are produced in the growth medium in either the presence or absence of serum. The concentrated inhibitor, although very unstable, gives up to a 50% inhibition of thymidine incorporation when assayed on sparse or crowded alveolar type II cells.

CONTROL OF GROWTH OF MAMMALIAN CELLS

Abstract: Factors that control the initiation of DNA synthesis in mouse embryo 3T3 cells and in small lymphocytes are reviewed. It is concluded that a wide variety of different substances can be active. Many of these substances presumably act on the cell membrane. The possible roles of cyclic nucleotides and membrane properties are discussed.