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Role of natural prostaglandins in the control of murine mammary tumor virus expression

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC). oligo(dG) as templateprimer. Two days after exposure, the synthetic clucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 μmol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1>PGE1>PGB1>PGF2α. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virusstimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormonelike substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.

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Abbreviations

AMP:

adenosine 3′,5′-monophosphate

cAMP:

adenosine 3′,5′-monophosphate, cyclic

db-cAMP:

dibutyryl-adenosine 3′5′-monophosphate, cyclic

DNA:

deoxyribonucleic acid

DXMT:

dexamethasone

ETYA:

eicosa-5,8, 11, 14-tetrayonic acid

MEM:

minimum essential medium

PGA:

prostaglandin A1

PGB1 :

prostaglandin B1

PGE1 :

prostaglandin E1

PGF2α:

prostaglandin F2 alpha

RNA:

ribonucleic acid

TCA:

trichloroacetic acid

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Authors and Affiliations

  1. Cancer Research Institute, Slovak Academy of Sciences, Csl. armady 21, CSSR-880 32, Bratislava, Czechoslovakia

    J. Svec & V. Thurzo

  2. Dept. of Pharmacology, Faculty of Pharmacy, Komensky University, Bratislava, Czechoslovakia

    P. Svec

  3. Dept. of Biochemistry, Faculty of Medicine, Komensky University, Bratislava, Czechoslovakia

    L. Halcak

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  1. J. Svec
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  2. P. Svec
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  3. L. Halcak
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  4. V. Thurzo
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Svec, J., Svec, P., Halcak, L. et al. Role of natural prostaglandins in the control of murine mammary tumor virus expression. J Cancer Res Clin Oncol 103, 55–67 (1982). https://doi.org/10.1007/BF00410306

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  • DOI: https://doi.org/10.1007/BF00410306

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