Cell cycle regulation by growth factors and nutrients in normal and transformed cells

Paul, Dieter; Brown, Kenneth D.; Rupniak, H. T.; Ristow, H. J.

doi:10.1007/bf02618176

Cited by 19 publications

(5 citation statements)

References 50 publications

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“…ODC activity is also increased after a variety of mitogenic stimulations (15,26,30,67), although there are exceptions (53,55 (21), and this could be another instance. c-ras and 2A9 have also been shown to be expressed in a cell cycle-dependent manner (13,27,28,31) in rat liver and cells in culture.…”

Section: Methodsmentioning

confidence: 98%

Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum.

Liu¹,

Baserga²,

Mercer³

1985

Mol. Cell. Biol.

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We have studied a panel of 10 genes and cDNA sequences that are expressed in a cell cycle-dependent manner in different types of cells from different species and that are inducible by different mitogens. These include five sequences (c-myc, 4F1, 2F1, 2A9, and KC-1) that are preferentially expressed in the early part of the G, phase, three genes (ornithine decarboxylase, p53, and c-rasHa) preferentially expressed in middle or late G1, and two genes (thymidine kinase and histone H3) preferentially expressed in the S phase of the cell cycle. We have studied the expression of these genes in nonpermissive (tsAF8) and semipermissive (Swiss 3T3) cells infected with adenovirus type 2. Under the conditions of these experiments, adenovirus type 2 infection stimulates cellular DNA synthesis in both tsAF8 and 3T3 cells. However, four of the five early GI genes (c-myc, 4F1, KC-1, and 2A9) and one of the late G, genes (c-ras) are not induced by adenovirus infection, although they are strongly induced by serum. The other sequences (2F1, ornithine decarboxylase, p53, thymidine kinase, and histone H3) are activated by both adenovirus and serum. We conclude that the cell cycle-dependent genes activated by adenovirus 2 are a subset of the cell cycle-dependent genes activated by serum. The data suggest that the mechanisms by which serum and adenovirus induce cellular DNA synthesis are not identical.Cell cycle-dependent genes are operationally defined here as genes that are preferentially expressed in a specific phase of the cell cycle. A number of animal genes have already been identified whose expression is cell cycle dependent. These include histone genes (2, 22, 57), c-myc (13, 28, 35, 49; B. Calabretta, L. Kaczmarek, W. Mars, D. Ochoa, C. W. Gibson, R. R. Hirschhom, and R. Baserga, Proc. Natl. Acad. Sci. USA, in press), c-ras (13,27,28), and c-fos (18,29,38) and genes encoding p53 (48, 60), actin (13,29,46) serum and that adenovirus infection preferentially activates genes whose expression reaches a maximum in the late G1-S phase. MATERIALS AND METHODSCell line and culture conditions. tsAF8 cells are G1-specific, temperature-sensitive mutants originally isolated from BHK cells (12); these cells have been extensively characterized (3,12,25). Monolayer cultures are routinely maintained in Dulbecco modified Eagle medium containing 10% (vol/vol) donor calf serum at the PT of 34°C. To obtain quiescent (Go) cultures, tsAF8 cells are plated at 106 cells per 100-mm plate, grown to near confluence at 34°C, rinsed twice with prewarmed Hanks salt solution, fed with medium containing 0.5% (vol/vol) donor calf serum, and incubated for an additional 48 h at 34°C. Swiss 3T3 cells were cultured and made quiescent as previously described (47).Virus propagation, purification, and infection. Ad2 was grown in HeLa suspension cultures maintained in minimum essential modified suspension medium (Flow Laboratories, Rockville, Md.) with 5% fetal calf serum. Virus was purified as described previously (63)

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Section: Methodsmentioning

confidence: 98%

Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum.

Liu¹,

Baserga²,

Mercer³

1985

Mol. Cell. Biol.

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“…Under our culture conditions, the doubling time and saturation density for the 3T3 cells were 22 h and 4-5 x 10' cells/cm', respectively (see reference 21). The cells were passaged by dislodging them from the growth surface using a 0.25% trypsin (Nutritional Biochemicals, Cleveland, Ohio) solution in phosphate-buffered saline (PBS) containing 4 x 10-°M versene .…”

Section: Cell Culturementioning

confidence: 99%

Growth control in cultured 3T3 fibroblasts. Assays of cell proliferation and demonstration of a growth inhibitory activity.

Steck

Voss

Wang³

1979

The Journal of Cell Biology

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Treatment of sparse, proliferating cultures of 3T3 cells (target cells) with medium conditioned by exposure to density-inhibited 3T3 cultures resulted in an inhibition of growth and division in the target cells when compared to similar treatment with unconditioned medium (UCM) . This differential effect of conditioned medium (CM) and UCM on target cells was demonstrated using three assay systems : (a) assessment of total cell number; (b) measurement of [ 3H]thymidine incorporated into acid-precipitable DNA; and (c) determination of the percentage of radioactively labeled nuclei in individual cells after incorporation of [3 H]thymidine. The difference in the total incorporation of [3 H]thymidine in CM-treated and UCMtreated cells was reflected by a difference in the percent oflabeled cells . There was no difference in the average number of grains per labeled cell in the two cultures . Moreover, the inhibitory effect of the CM on target cell proliferation was reversible. Finally, this growth inhibitory activity can be collected in serum-free medium, precipitated by ammonium sulfate, and fractionated by gel filtration . In these purification procedures, the inhibitory activity was consistently found to be associated with the protein-containing fractions of the CM . No activity was found upon similar treatment with UCM . These results suggest that a system has been developed for the purification and molecular analysis of growth inhibitory factors that may mediate growth control in culture fibroblasts .

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“…It was also reported some time ago that in 3T3-4a cells stimulated by serum a significant proportion (more than 30%) of stimulated cells do not show increases in RNA levels although entering S-phase with the same kinetics as cells with increased RNA content (Paul et al, 1978). It has also been reported that 3T3 cells that traverse the cell cycle in low serum undergo DNA replication and mitosis at a reduced size.…”

mentioning

confidence: 90%

Immediate effects of serum depletion on dissociation between growth in size and cell division in proliferating 3T3 cells

Larsson

Dafgård

Engström

et al. 1986

Journal Cellular Physiology

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Proliferating nonconfluent 3T3 cells become committed to proceed through the cell cycle or to enter G0 during the first post-mitotic part of G1 (G1pm). The decision to proceed through G1pm is dependent on the presence of serum growth factors in the culture medium. Cells that have passed this particular growth-factor-dependent cell cycle stage are independent of serum growth factors and undergo mitosis on schedule. We report here that G1ps, S, and G2 cells cease to increase in size when serum is withdrawn. As a result the mitotic cell size after 8 hours serum starvation is reduced to approximately 60% of the normal mitotic cell. This reduced growth in cell size is due to a rapid decrease in protein synthesis and some increase in protein degradation. This dissociation between growth in size and cell-cycle progression within a single cell cycle provides a new approach to study the two processes separately.

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Cell cycle regulation by growth factors and nutrients in normal and transformed cells

Cited by 19 publications

References 50 publications

Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum.

Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum.

Growth control in cultured 3T3 fibroblasts. Assays of cell proliferation and demonstration of a growth inhibitory activity.

Immediate effects of serum depletion on dissociation between growth in size and cell division in proliferating 3T3 cells

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