Cyclic AMP-mediated transformation of rat cells transformed by temperature-sensitive mouse sarcoma virus

Somers, Kenneth D.; Rachmeler, Martin; Christensen, Mary

doi:10.1038/257058a0

Cited by 11 publications

(3 citation statements)

References 20 publications

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“…That these phenotypic changes are associated with the transformation process has been demonstrated with the aid of ts viral mutants (39). Cells infected with the (29). Thus, based on morphological criteria, cells acquired the transformed phenotype either by a temperature shift to the permissive condition or by the addition of cAMP.…”

Section: Discussionmentioning

confidence: 99%

“…The proposal that transformed cells are highly agglutinable because their low cAMP levels result in the formation of numerous surface microvilli is not supported by our data. NRK(MSV-lb) cells grown under conditions permissive for expression of the transformed phenotype have elevated levels of endogenous cAMP (29), numerous surface membrane blebs and microvilli (34), and an increased agglutinability relative to the cells grown under restrictive conditions. Furthermore, the acquisition of the transformed morphology without an increase in agglutinability after cAMP treatment of NRK(MSV-lb) cells at 33~ indicates that cAMPmediated morphological alterations are not necessarily associated with altered agglutinability.…”

Section: Discussionmentioning

confidence: 99%

“…supplemented with 10% fetal calf serum. Cells were exposed to 0.4 mM 8-bromo cyclic AMP (8BrcAMP; ICN Pharmaceuticals, Inc., Irvine, Calif.) without replacing the growth medium as previously described (29). For morphological studies, cells were seeded at 5-8 • 105 per 60-mm Petri dish, incubated for 2 days, exposed to 8BrcAMP, and examined with a Zeiss phase-contrast microscope.…”

Section: And Included (A) Nrk Cells (B) Nrk Cells Transformed and Prmentioning

confidence: 99%

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Cyclic amp-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus: Expression of transformation-associated markers

Kalina¹,

Pease²

1977

The Journal of Cell Biology

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Normal rat kidney (NRK) cells infected with a temperature-sensitive (ts) mutant of mouse sarcoma virus (NRK [MSV-lb]) express the transformed phenotype under permissive conditions, but acquire the normal phenotype when grown under restrictive conditions. Addition of 3',5' cyclic adenosine monophosphate (cAMP) to NRK(MSV-lb) cells grown at the restrictive temperature results in morphological transformation. To determine whether other markers associated with the transformed phenotype were coordinately expressed after cAMP exposure, concanavalin A (Con A) agglutinability, hexose transport rate, and incorporation of radioactively labeled fucose into fucolipid III and fucolipid IV (FL III and FL IV) of the cells were examined. NRK cells transformed by wild-type MSV or NRK(MSV-lb) grown under permissive conditions were agglutinated by low concentrations of Con A and exhibited relatively high maximal agglutination levels which were specifically inhibited by a-methyl-D-mannoside. In contrast, NRK(MSV-lb) cells grown under restrictive conditions were weakly agglutinated by Con A and exhibited reduced maximal agglutination levels, similar to uninfected NRK cells. Treatment of NRK(MSV-lb) cells at the restrictive temperature with cAMP resulted in morphological transformation and a change in the pattern of incorporation of labeled fucose into FL III and FL IV to one comparable to that of NRK(MSV-lb) cells at the permissive temperature or to NRK cells transformed by wild-type MSV. In contrast, cAMP treatment resulted in no increase in Con A agglutinability or 2-deoxy-o-[aH]glucose transport relative to mock treated cultures. The results demonstrate that cAMP-induced morphological transformation and altered fucolipid composition of NRK(MSV-lb) cells are not correlated with alterations in hexose transport rate or Con A agglutinability.We have recently reported (29) that 3',5' cyclic adenosine monophosphate (cAMP) affects the morphological transformation of normal rat kidney (NRK) cells transformed by a temperaturesensitive (ts) mutant of mouse sarcoma virus (MSV). Expression of the transformed phenotype TUE JOURNAL OF CELL BIOLOGY 9 VOLUME 74, 1977 9 pages 707-716 707

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: And Included (A) Nrk Cells (B) Nrk Cells Transformed and Prmentioning

confidence: 99%

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Cyclic amp-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus: Expression of transformation-associated markers

Kalina¹,

Pease²

1977

The Journal of Cell Biology

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Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes

et al. 1976

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It is shown that cyclic nucleotides can have a variety of effects on cell division, cell shape, cell adhesion, and cell movement, depending on the cells selected and the conditions under which they are used. For example, while CHO cells elongate under the influence of exogenous dibutyryl CAMP, Y-1 adrenal tumor cells round up and polyoma-transformed 3T3 cells show no change in shape. The totality of experience with cyclic nucleotides suggests that where they have been used by cells as control elements involving the four processes listed above, they are superimposed on basic cellular processes that progress in their absence--that is, they must be acting indirectly. In attempting to understand the inhibitory action of methyl xanthines on egg development, we were forced to abandon the idea that they acted through cyclic nucleotides. We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors. Further, we found that tubulin polymerizability, NAD-kinase activity, and a mitotic apparatus associated Ca+2-ATP-ase were all inhibited by oxidation of some of their sulfhydryls and were activated by reduction of the resulting disulfides. These results are discussed in terms of reported cycles and activations of glutathione reductase (GR) in cells and reports that mixed disulfides of glutathione and proteins can act as substrates for GR. Using the fact that a CAMP-dependent protein kinase has been reported to be activated by glutathione, we have suggested potential sites where sulfhydryl control processes and cyclic nucleotide control processes and cyclic nucleotide control processes may interact in certain restricted cases.

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Increased cyclic AMP content directly correlated with morphological transformation of cells infected with a temperature-sensitive mutant of mouse sarcoma virus

Somers

1980

In Vitro

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Normal rat kidney cells infected with a cold-sensitive mutant of mouse sarcoma virus [NRK(MSV-lb)] morphologically transform when exposed to adenosine 3':5' cyclic monophosphate (cAMP) at the restrictive temperature. The cAMP-induced morphological changes occur rapidly and are reversible. Agents capable of elevating endogenous levels of cAMP [prostaglandin E1 (PGE1) and cholera toxin (CT)] induced morphological transformation of NRK(MSV-lb) cells at the restrictive temperature that was concentration dependent, potentiated by cAMP phosphodiesterase inhibitors, and not prevented by inhibitors of DNA, RNA, and protein synthesis. Prostaglandin E1 stimulated a transient increase in the intracellular level of cAMP with a concomitant morphological transformation and reversion of cells as cAMP levels decline. The maximum increase is reached by 10 min, followed by a decline to near basal level by 80 min. In contrast, incubation of cells with CT resulted in irreversible morphological transformation and increased levels of cAMP first detectable by 1 hr with maximum levels reached by 24 hr. Heated CT (100 degrees C, 20 min) was without effect. Addition of CT to reverted PGE1-treated cells resulted in morphological transformation suggesting the existence of discrete receptors in NRK(MSV-lb) cells.

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Cyclic AMP-mediated transformation of rat cells transformed by temperature-sensitive mouse sarcoma virus

Cited by 11 publications

References 20 publications

Cyclic amp-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus: Expression of transformation-associated markers

Cyclic amp-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus: Expression of transformation-associated markers

Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes

Increased cyclic AMP content directly correlated with morphological transformation of cells infected with a temperature-sensitive mutant of mouse sarcoma virus

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