Biomedical subjects

P V Cherington

Publications and source records attributed to P V Cherington.

4 recordsLinked to original sources

PubMed1983

Clonal analysis of a 5-azacytidine-induced specific increase in growth hormone production by rat pituitary cells.

The nucleoside analog, 5-azacytidine (5-azaCR) which causes genomic hypomethylation in many cell types, increased GH production by GH4C1 rat pituitary cells 3-5 fold. This increased GH production was independent of changes in prolactin (PRL) synthesis by the same cells; it occurred at 10-fold lower 5-azaCR concentrations than those which increased the synthesis of PRL. Elevated GH production persisted for more than 20 population doublings after removal of 5-azaCR from the culture medium, indicating that the induced change was phenotypically stable. GH production remained responsive to stimulation by cortisol in 5-azaCR-treated cells. Clonal analysis demonstrated that the increased GH production was due to a higher incidence of cells in the population which made GH at an enhanced rate.

Animals↗

PubMed1981

On deciding which factors regulate cell growth.

Many conditions affect the growth of animal cells in culture. Some, such as essential nutrients, are necessary for growth as precursors of macromolecules. Other substances appear to have regulatory functions. Their presence or absence determines whether the cell will continue to grow or move into a resting, quiescent state. In particular certain factors (usually provided by serum) are thought to have regulatory roles. To decide which factors are regulatory is a difficult problem. We propose here that no single criterion is sufficient to permit a decision and that the best course at present is to apply several criteria. Three such criteria are proposed. To the degree that the tests are satisfied we can tentatively decide whether or not a given factor is regulatory.

Animals↗

PubMed1980

Synergistic effects of epidermal growth factor and thrombin on the growth stimulation of diploid Chinese hamster fibroblasts.

The serum supplement used in the culture of a variety of mammalian cells can be replaced by known growth factors. Diploid Chinese hamster fibroblasts (CHEF/18) will grow for several days in a medium (4F) supplemented with four growth factors: epidermal growth factor (EGF), insulin, fibroblast growth factor (FGF), and transferrin. The growth rate is only about 50% as fast as when fetal calf serum is added. This difference is eliminated by thrombin (10--100 ng/ml; 0.3--3 nM). The CHEF/18 cell line is unique in that no other cell line responds to thrombin in this concentration range. Thrombin acts synergistically with other growth factors to stimulate CHEF/18 cell growth. By itself, thrombin is only mitogenic at elevated concentrations. Thrombin can largely compensate for the absence of EGF and partly for the absence of insulin in serum-free media. Chemically and "spontaneously" transformed cell lines related to CHEF/18 have lost requirements for both EGF and thrombin, and have retained requirements for insulin and transferrin expressed by CHEF/18. No CHEF cells in this work required FGF. These results suggest that the mechanisms by which EGF and thrombin stimulate cells to grow are related.

Animals↗

PubMed1979

Loss of epidermal growth factor requirement and malignant transformation.

Serum provides growth factors that regulate and limit the growth of normal cells in tissue culture. Animal cells that are malignantly transformed usually exhibit diminished serum requirements for growth in culture. We have used a defined, serum-free medium to determine which of these growth factors becomes dispensable for the growth of transformed Syrian and Chinese hamster fibroblast cells. The medium's four growth factors-epidermal growth factor (EGF), insulin, fibroblast growth factor, and transferrin-were added or omitted as desired. A decreased requirement for EGF was most closely related to tumorigenicity of chemically (ethyl methanesulfonate) transformed cells in nude mice. All lines examined retained their requirement for transferrin, which is needed throughout the growth cycle, in contrast to the other factors, which are needed primarily in G(1) phase. Lines that had lost their EGF requirement but had retained their insulin requirement were arrested in G(1) by insulin deficiency, indicating that their growth control system remained. Mutagenesis with ethyl methanesulfonate can also create requirements of the transformed cells for unknown factors in serum. We conclude that an initial step that reduces the serum requirement in culture, and in tumorigenesis, is relaxation of the growth-regulatory function of EGF.

Blood↗