Hormone-treated cho cells exit the cell cycle in the G2 phase

Remington, John A.; Klevecz, Robert R.

doi:10.1016/0006-291x(73)91075-9

Cited by 23 publications

(4 citation statements)

References 16 publications

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“…This has been variously reported as lying in G1 (7,13,14), in G2 (8), or in multiple discrete portions of the cycle (15,16). These studies have in most cases used cell populations synchronized by techniques that possibly cause unbalanced growth, which might raise questions regarding the use of these materials for examining the effect of a growth regulatory substance.…”

mentioning

confidence: 99%

Cyclic AMP, a nonessential regulator of the cell cycle.

Coffino

Gray

Tomkins

1975

Proc. Natl. Acad. Sci. U.S.A.

101

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Flow-microfluorimetric analysis has been carried out on populations of exponentially growing S49 mouse lymphoma cells treated with dibutyryl cyclic AMP./The drug produces a specific concentration-dependent kblock in the GI phase of the cell cycle while other phases of the cycle are not perceptibly altered. The cell cycle of a line of mutant cells lacking the cyclic AMP-dependent protein kinase is not affected by the drug. Since these mutant cells have been shown to maintain a normal cell cycle, even in the presence of high levels of cyclic AMP, periodic fluctuations in the levels of the cyclic nucleotide cannot be required for or determine progression through the cell cycle.There is considerable evidence that adenosine 3': 5'-cyclic monophosphate (cAMP) has a regulatory effect on the growth of cells in culture. The levels of the cyclic nucleotide increase as untransformed cells approach confluency (1,2), although this is contradicted by others (3). Intracellular cAMP concentrations are negatively correlated with growth rate among a variety of fibroblast cell lines (4). Transformed cells have a lower cAMP content than untransformed cells (1, 5). Exogenous cAMP analogs or the induction of endogenous cAMP slows or stops growth of some cells (6-10). Proliferation of contact-inhibited cells, induced by refeeding or proteolytic treatment, is prevented by cAMP analogs (7,11). The cAMP level changes during the cell cycle and is specifically low in mitosis (11,12).While these results make it clear that cAMP can cause marked effects on the cell cycle, important questions remain unanswered.(i) Is cAMP merely a negative regulator of the cycle, or is variation of cellular cAMP levels a necessary signal that entrains the cell cycle? Burger et al. (11) have proposed, for instance, that a fall in cAMP is the signal that necessarily precedes DNA synthesis.(ii) What is the locus of the growth-inhibitory action of cAMP? This has been variously reported as lying in G1 (7,13,14), in G2 (8), or in multiple discrete portions of the cycle (15, 16). These studies have in most cases used cell populations synchronized by techniques that possibly cause unbalanced growth, which might raise questions regarding the use of these materials for examining the effect of a growth regulatory substance.To answer these questions we have studied growth regulation in cultured S49 mouse lymphoma cells. These cells are advantageous because growth of wild-type populations is inhibited by cAMP, and cAMP-insensitive mutants can be derived that are defective in the cAMP binding protein and its associated protein kinase (17,18). In the present studies we have used the flow-microfluorimeter (19)

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mentioning

confidence: 99%

Cyclic AMP, a nonessential regulator of the cell cycle.

Coffino

Gray

Tomkins

1975

Proc. Natl. Acad. Sci. U.S.A.

101

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“…In the presence of db-CAMP, CHO V79 cells accumulated in Gz (Stambrook and Velez, 1976). Similarly, CHO cells treated with db-cAMP and testosterone are arrested in Gz (Remington and Klevecz, 1973). db-CAMP blocked Cloudman melanoma cells in late S and Gz phases (Dipasquale and McGuire, 1977).…”

Section: Discussionmentioning

confidence: 91%

“…The process of reverse transformation is reversible when the inducing agent is removed from the medium. Furthermore, a number of published reports indicate that following exposure to db-CAMP, some transformed cell lines are arrested in the GI phase of the cell cycle (Willingham et al, 1972;Tee1 and Hall, 1973;Froehlich and Rachmeler, 1974;Leof et al, 1982) while others are blocked in the Gz or S period (Smets, 1972;Willingham et al, 1972;Remington and Klevecz, 1973;Stambrook and Velez, 1976;Dipasquale and McGuire, 1977).…”

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confidence: 99%

Induction of reverse transformation and normal cell cycle regulation by dibutyryl cAMP in a chemically transformed cell line

Wang

Rao

1983

Journal Cellular Physiology

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The objective of this study was to determine whether N6, O2-dibutyryl 3',5'-adenosine monophosphate (db-cAMP)-induced reverse transformation in a chemically transformed mouse cell line, AKR-MCA, would restore normal cell cycle regulation, particularly with regard to their growth arrest in the early G1 period. The AKR-MCA cells were grown to confluency in the presence or absence of db-cAMP (0.5 mM) plus theophylline (1 mM). The confluent cultures were trypsinized and a portion of the cells were fused with mitotic HeLa cells to induce premature chromosome condensation, while the remaining cells were used to study the kinetics of initiation of DNA synthesis. The prematurely condensed chromosomes (PCC) of the control and the treated cultures were classified into G1, S, or G2 types on the basis of their morphology. The G1 PCC were further subclassified into six groups (+1 - +6); +1 being the most condensed and +6 the most decondensed. The cyclic AMP (cAMP)-treated cells exhibited better attachment to the culture dish, were blocked in early G1 period at confluency, and entered S phase about 4 h later than the control following subculturing. In contrast, a majority of cells in the control cultures were arrested in S phase at confluency. These data indicate that the db-cAMP-induced reverse transformation in AKR-MCA cells at least partially restores normal cell cycle regulation in these chemically transformed cells.

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“…In addition, Bullough and Laurence (1964) have studied a tissue factor which can arrest cells in G, and prevent them from entering mitosis. In these cells too, there is an elevation of the levels of cyclic AMP (Remington and Klevecy, 1973). Nucleotide levels in fibroblasts exposed to LF have not been measured.…”

Section: Discussionmentioning

confidence: 99%

Regulation of growth of human diploid fibrobalasts by factors elaborated by activated lymphoid cells

Korotzer

Page

Granger

et al. 1982

Journal Cellular Physiology

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Fibroblasts growth synthesis activities appear to be under exquisite control. This control is mediated in part by substances present in blood plasma or released by other cells. We have studied the role of peripheral blood mononuclear cells (PBM) activated with phytohemagglutinin-P (PHA) on DNA synthesis, proliferation, and the cell cycle of human diploid fibroblasts. Culture medium from activated but not from unactivated PBM cultures inhibited fibroblast DNA synthesis and growth in a dose-dependent manner. The activity, which was designated as lymphocyte factor (LF), was very potent; it inhibited 50% of the DNA synthesis and cell growth at a dilution of 1:160. It has a molecular weight between 50,000 and 100,000 daltons and it is destroyed by trypsin digestion or by heating at 80 degrees C for 30 minutes. The activity was not due to the presence of prostaglandin. Furthermore, using immunoprecipitation and affinity chromatography, it was shown conclusively to to be distinctly different from alpha lymphotoxin (alpha-LT). It was not cytotoxic, as shown by the 51chromium release technique. Using flow microfluorimetry it was shown that the activity regulates fibroblast growth by preventing quiescent cells in the G0 or G1 stage of the cell cycle from entering the S phase. Cells already in S at the time of exposure complete DNA synthesis but cannot divide, and they accumulate in G2. The activity also has marked effects on protein synthesis. Activated mononuclear cells may play a major role in regulating fibroblast growth and synthesis in normally healing wounds and in acute and chronic inflammatory processes.

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Hormone-treated cho cells exit the cell cycle in the G2 phase

Cited by 23 publications

References 16 publications

Cyclic AMP, a nonessential regulator of the cell cycle.

Cyclic AMP, a nonessential regulator of the cell cycle.

Induction of reverse transformation and normal cell cycle regulation by dibutyryl cAMP in a chemically transformed cell line

Regulation of growth of human diploid fibrobalasts by factors elaborated by activated lymphoid cells

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