Reduced Adenyl Cyclase Activity in a Polyoma Virus Transformed Cell Line

Bürk, R. R.

doi:10.1038/2191272a0

Cited by 216 publications

(38 citation statements)

References 13 publications

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“…Johnson contact-inhibition and morphology of normal cells and stimulates collagen synthesis in these fibroblasts (10,11). Polyoma virus-transformed fibroblasts contain less adenylate cyclase activity than do untransformed fibroblasts (12). These observations suggest that cAMP may play an important role in the regulation of the growth of these cells, in addition to the well-documented role as the intracellular mediator of hormonal actions.…”

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confidence: 63%

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Inhibition of Replication in Functional Mouse Adrenal Tumor Cells by Adrenocorticotropic Hormone Mediated by Adenosine 3′:5′-Cyclic Monophosphate

Masui

Garren

1971

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

125

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mentioning

confidence: 63%

“…The incorporation was inhibited by more than 90% in 14 hr and remained low for another 12 hr. In control experiments, in which cells were incubated in the absence of ACTH,…”

Section: Resultsmentioning

confidence: 94%

Inhibition of Replication in Functional Mouse Adrenal Tumor Cells by Adrenocorticotropic Hormone Mediated by Adenosine 3′:5′-Cyclic Monophosphate

Masui

Garren

1971

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

125

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“…However, in another study, Burk (1) showed that the growth of normal BHK cells and RSVtransformed BHK cells was greatly inhibited by 2 mm theophylline while the growth of polyomatransformed BHK cells was not . Furthermore, he found that normal BHK cells and RSV-transformed BHK cells contained more adenyl cyclase activity in their membranes than the polyomatransformed cells.…”

Section: Kinetics Of Irreversible Commitment To Dna Synthesismentioning

confidence: 99%

“…Cells of malignant origin contain either very low or no membrane adenyl cyclase activity (11,17) ; and baby hamster kidney (BHK) cells transformed by polyoma virus appear to have less adenyl cyclase activity than the untransformed parental cell line (1) . In addition, the proliferation of L cells and HeLa cells (26) is inhibited by exogenous cAMP .…”

Section: Introductionmentioning

confidence: 99%

Effect of Adenosine 3'-5'-Cyclic Monophosphate on Cell Proliferation

Froehlich

Rachmeler

1972

The Journal of Cell Biology

140

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Secondary cultures of human diploid fibroblasts, which demonstrate density-dependent inhibition of cell growth, were used to study the effect of adenosine 3'-5'-cyclic monophosphate (cAMP) on cell proliferation. DNA synthesis in nonconfluent cultures and in contact-inhibited cultures stimulated to grow by refeeding with fresh medium was found to be inhibited by exogenous cAMP. The properties of this inhibition of DNA synthesis, together with the alterations in cAMP metabolism observed in confluent cultures of cells stimulated with fresh medium to resume growth, strongly suggest that cAMP is involved in contact-inhibition of cell proliferation.

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“…In the meantime, numerous reports have implicated cAMP as a regulator of growth, morphology, and contact inhibition in cultured cells (6)(7)(8)(9)(10)(11). We report here that altering the in- Intracellular cAMP concentrations were assayed by Gilman's method (14).…”

mentioning

confidence: 99%

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

Kram

Mamont

Tomkins

1973

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

145

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The effects of serum deprivation on several general cellular biochemical processes ("pleiotypic response") related to the growth of normal fibroblasts can be mimicked by treatment of these cells with prostaglandin El in the presence of serum. N8,02'-Dibutyryl adenosine 3': 5'-cyclic monophosphate and theophylline inhibit the membrane transport processes without much effect on other pleiotypic reactions such as overall protein and RNA synthesis and protein degradation. The amount of intracellular cyclic AMP increases during serum starvation and returns to the initial concentration in unstarved cells when growth is initiated again upon addition of serum. Fibroblasts transformed by simian virus 40 have a lower cyclic AMP content than their untransformed parents. Serum deprivation neither increases cyclic AMP content nor significantly affects the pleiotypic reactions in transformed cells. Cycloheximide causes a decrease in cyclic AMP content of normal fibroblasts coincidentally with the ability of this inhibitor to stimulate uridine transport and slow protein degradation in cells deprived of serum.In normal cells, several biochemical parameters, including membrane transport, overall rates of protein and RNA synthesis, and protein degradation, fluctuate coordinately with changes in cell-growth rate. These mechanistically unrelated processes and their coordinated response to environmental changes comprise what we have defined as the "pleiotypic program" and "pleiotypic control," respectively. In malignant cells, the pleiotypic program and the rate of growth are relatively insensitive to changes in cultural conditions; we thus picture transformed cells as having a defect in the pleiotypic control mechanism (1).In cultured fibroblasts, insulin as well as serum activates the pleiotypic program (1, 2). Moreover, the same set of reactions is regulated in many other cell types by specific hormones or growth factors. Thus, certain general features of hormonal regulation may also be exerted through the pleiotypic mechanism (1).We have postulated that a "mediator", probably formed at the cell membrane, coordinates the responses of the different reactions under pleiotypic control. Because of the resemblance of this regulatory program to "stringent control" in bacteria, we inquired whether guanosine 5'-diphosphate, 2'-or 3'-diphosphate (ppGpp) (a possible mediator of stringent control) (3, 4) could be involved in control in animal cells. However, this nucleotide was not detected in cultured 3T3 cells under conditions that should have elicited its appearance (5).In the meantime, numerous reports have implicated cAMP as a regulator of growth, morphology, and contact inhibition in cultured cells (6-11). We report here that altering the inAbbreviations: Bu2cAMP, N6,02'-dibutyryl adenosine 3':5'-cyclic monophosphate; PGE,, prostaglandin El; SV40, simian virus 40. tracellular cAMP content by various means can affect all the reactions under pleiotypic control in a way, suggesting that cAMP is very likely the pleiotypic mediator...

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Reduced Adenyl Cyclase Activity in a Polyoma Virus Transformed Cell Line

Cited by 216 publications

References 13 publications

Inhibition of Replication in Functional Mouse Adrenal Tumor Cells by Adrenocorticotropic Hormone Mediated by Adenosine 3′:5′-Cyclic Monophosphate

Inhibition of Replication in Functional Mouse Adrenal Tumor Cells by Adrenocorticotropic Hormone Mediated by Adenosine 3′:5′-Cyclic Monophosphate

Effect of Adenosine 3'-5'-Cyclic Monophosphate on Cell Proliferation

Pleiotypic Control by Adenosine 3′:5′-Cyclic Monophosphate: A Model for Growth Control in Animal Cells

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