Dibutyryl Cyclic Adenosine 3' 5' Monophosphate, Sugar Transport, and Regulatory Control of Cell Division in Normal and Transformed Cells

Grimes, William J.; Schroeder, Judith L.

doi:10.1083/jcb.56.2.487

Cited by 53 publications

(5 citation statements)

References 21 publications

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“…Thus addition of N6,2'-O-dibutyryl cyclic AMP, particularly with theophylline, to transformed cells has been reported to restore density-dependent inhibition of cell growth (Hsie & Puck, 1971;Sheppard, 1971). However, other workers have found that the inhibition of growth this causes differs from that in dense cultures of normal cells (Paul, 1972;Smets, 1972;Grimes & Schroeder, 1973;Van Wijk et al, 1973). Zacchello et al (1972 reported that the adenylate cyclase activity per mg of cell protein in human diploid fibroblasts increases during growth to confluence.…”

Section: Discussionmentioning

confidence: 93%

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Haslam

Goldstein

1974

Biochemical Journal

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Cyclic AMP levels per mg of cell protein were higher in late-passage (senescent) fibroblasts than in early-passage (young) fibroblasts both during growth and stationary phase, but, because the protein concentration per unit volume in senescent cells was lower than in young cells, the molar concentrations of intracellular cyclic AMP were very similar in the two cell types. In both young and senescent fibroblasts cyclic AMP levels declined during growth and no increase in intracellular cyclic AMP occurred in association with density-dependent inhibition of growth. These results indicate that changes in cyclic AMP concentration do not play a role in controlling the growth or in the senescent decline of human fibroblasts. Prostaglandin E(1) (1mum) caused maximal increases in fibroblast cyclic AMP concentration of 60-500-fold after 10-30min, and adrenaline (epinephrine) (10mum) caused maximum increases of 5-25-fold after 2-10min, depending on both the number of passages and the period after subculture. The cyclic AMP level in confluent young cells increased more with prostaglandin E(1) and far less with adrenaline than the cyclic AMP level in confluent senescent cells. During growth to confluence the cyclic AMP response to adrenaline declined in young cells and increased in senescent cells. As these responses to prostaglandin E(1) and to adrenaline changed independently of each other and of the basal cyclic AMP concentration, it is suggested that the expression of hormone receptors is altered both during growth to confluence and during senescence of human fibroblasts.

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Section: Discussionmentioning

confidence: 93%

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Haslam

Goldstein

1974

Biochemical Journal

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“…Theophylline, which elevates intracellular cyclic AMP by blocking its degradation, had a similar growth inhibiting effect. It is known that cyclic AMP regulates growth of certain cells [23,24]. In a parallel study, theophylline similarly depressed the growth of normal fibroblasts (data not shown).…”

Section: Discussionmentioning

confidence: 60%

Cultured breast cystosarcoma phylloides cells and applications to patient therapy

Lewko¹,

Vaghmar²,

Maleckar³

et al. 1990

Breast Cancer Res Tr

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Malignant cystosarcoma phylloides (CP) is a relatively rare cancer of the breast. A CP tumor was processed as part of a tumor acquisition, propagation, and preservation program in patient biotherapy. Two tissue culture cell lines were developed from this tumor, one directly from the biopsy, another from a xenograft tumor grown in athymic mice. The two cell lines were similar in character. There was strong immunochemical reactivity with antibodies to vimentin, type I collagen, and type III collagen. There was no reactivity with antibodies to cytokeratin and epithelial membrane antigen. Both cell lines were aneuploid, clonogenic in soft agar, and tumorigenic in nude mice. 5 alpha-dihydrotestosterone and thyroxine added to the culture medium stimulated growth, while testosterone, 17 beta-estradiol, and 4-hydroxytamoxifen were without effect. Dexamethasone and cortisol were inhibitory at high doses (10(-6) M). Dibutyryl cyclic AMP, theophylline, and vitamin C were all inhibitory. The biopsy contained tumor-infiltrating lymphocytes which proliferated in cultures containing interleukin 2. The expanded lymphocytes were activated T cells which had the capacity to lyse tumor cells. These results suggest possibilities in the therapy of cystosarcoma phylloides involving vitamin C, certain hormones, and tumor-infiltrating lymphocytes.

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“…The effects of cyclic AMP on the multiplication oftransformed cells are different from those produced by limiting the concentration of Mg2+. In one case it was reported that the addition of cyclic AMP limits the number of cell generations regardless of the initial density (12), and in another it was reported that growth on solid surfaces is unchanged by cyclic AMP (13 …”

Section: Resultsmentioning

confidence: 99%

Growth regulation, reverse transformation, and adaptability of 3T3 cells in decreased Mg ²⁺ concentration

Rubin¹

1981

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

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A nontransformed and a spontaneously transformed clone of BALB/c 3T3 cells were compared for their capacity to multiply in decreased concentrations of Mg2e. Cells of the nontransformed clone were flat, formed regularly patterned, nonoverlapping arrays, required high serum concentration for multiplication, had a low saturation density, and did not make colonies in agar. Cells of the transformed clone were slender and spiky, formed random, overlapping arrays, multiplied in low serum concentrations, and had no fixed saturation density, and 20-30% of them formed colonies in agar. The When animal cells in culture are treated with growth stimulants such as insulin or serum, various reactions in the cells are accelerated (1). This group of cellular reactions has been designated "the coordinate response" (2, 3). Many of the early reactions of the coordinate, response are independent of one another and of macromolecular synthesis (1). The only intracellular substance that has the capacity, both theoretically and experimentally, to modulate the various reactions of the coordinate response is Mg2", and I have proposed that Mg2+ acts as a second messenger for these growth stimulants (2, 3). McKeehan and coworkers concurred in this conclusion and additionally proposed that cell transformation causes a selective loss ofthe regulatory role ofMg2+ (4, 5). Their conclusions were based on measurements of the size of colonies of normal and transformed cells formed in varying concentrations ofMg2+ and in other putative growth regulatory substances.I set out to extend their findings by comparing the effects of exposure to different concentrations ofMg2+ on growth rate and saturation density of a nontransformed clone of 3T3 cells and a spontaneously occurring transformed variant of that line. I found that the differential requirements' ofthe two cell lines for Mg2+ depend on a complex set of variables which will be described elsewhere. The experiments did show a consistent relationship between the initial multiplication rate of nontransformed cells and their saturation density, which clarifies the relative contributions of growth stimulatory materials and population density in fixing limits to the size of a population. Deprivation of Mg2`caused the transformed cells to resemble nontransformed cells in appearance and growth behavior. After about 1 week in Mg2+-deficient medium, the rate of DNA synthesis began an increase which continued through the second week in both nontransformed and transformed cells, and the latter reverted to their original appearance. MATERIALS AND METHODSCell Types, Transfers, and Labeling Techniques. The original cells used in these experiments were of the A31 clone of BALB/c 3T3 cells which had been recloned by J. Bartholomew to obtain a uniform culture of flat cells. This "parental clone" was obtained in January 1979 and maintained by weekly transfers at low population density in Dulbecco's modification of Eagle's medium containing 10% calf serum in the early passages and 10% fetal calf serum lat...

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Dibutyryl Cyclic Adenosine 3' 5' Monophosphate, Sugar Transport, and Regulatory Control of Cell Division in Normal and Transformed Cells

Cited by 53 publications

References 21 publications

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Cultured breast cystosarcoma phylloides cells and applications to patient therapy

Growth regulation, reverse transformation, and adaptability of 3T3 cells in decreased Mg ²⁺ concentration

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Dibutyryl Cyclic Adenosine 3' 5' Monophosphate, Sugar Transport, and Regulatory Control of Cell Division in Normal and Transformed Cells

Cited by 53 publications

References 21 publications

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Adenosine 3′:5′-cyclic monophosphate in young and senescent human fibroblasts during growth and stationary phase in vitro. Effects of prostaglandin E1 and of adrenaline

Cultured breast cystosarcoma phylloides cells and applications to patient therapy

Growth regulation, reverse transformation, and adaptability of 3T3 cells in decreased Mg 2+ concentration

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Growth regulation, reverse transformation, and adaptability of 3T3 cells in decreased Mg ²⁺ concentration