Virchows Archiv B

, 49:307 | Cite as

Heterogenous localization of adenylate and guanylate cyclases in R3230AC rat mammary adenocarcinoma cells

  • Bang H. Hwang
  • Dai Kee Liu


Adenylate and guanylate cyclase activities were demonstrated in R3230AC rat mammary adenocarcinomas by electron microscopic cytochemistry. Adenylate (AC) and guanylate (GC) cyclases were detected on plasma membrane of tumor epithelial cells, but not on fibroblasts and endothelial cells in the perivascular space. Both AC and GC activities were enriched in tumor epithelial cells at the periphery of the tumor lobular parenchyma rather than in cells in central core of the lobular parenchyma. Furthermore, the tumor cell plasma membranes facing the connective tissue stroma were in paucity or devoid of either enzyme activity. These heterogenous distributions of both AC and GC among tumor epithelia suggest that R3230AC epithelial cells in different parts of the tumor mass may vary significantly in their regulation of cellular physiology.

Key words

Mammary tumor Adenylate cyclase Cytochemistry 


  1. Adams AT (1984) Quantitative analysis of heterogeneity of estrogen binding in human breast tumor specimens. Anal Quant Cytol 6: 284–292PubMedGoogle Scholar
  2. Boynton AL, Whitfield JF (1983) The role of cyclic AMP in cell proliferation: A critical assessment of the evidence. Adv Cyclic Nucleotide Res 15: 193–294Google Scholar
  3. Cho-Chung YS (1980) On the mechanism of cyclic AMP-mediated growth arrest of solid tumors. Adv Cyclic Nucleotide Res 12: 111–121PubMedGoogle Scholar
  4. Cho-Chung YS, Clair T, Bodwin TS, Berghoffer B (1981) Growth arrest and morphological changes of human breast cancer cells by dibutyryl cyclic AMP and L-argine. Science 214: 77–79PubMedCrossRefGoogle Scholar
  5. Cohen LA, Chan P-C (1975) Intracellular cAMP levels in normal rat mammary gland and adenocarcinoma.In vivo vsin vitro. Life Sci 16: 107–115PubMedCrossRefGoogle Scholar
  6. Friedman DL (1976) Role of cyclic nucleotides in cell growth and differentiation. Physiol Rev 56: 652–708PubMedGoogle Scholar
  7. Goldberg ND, O’Dea RF, Haddox MK (1973) Cyclic AMP. Adv Cyclic Nucleotides Res 3: 155–223Google Scholar
  8. Granner D, Chase LK, Aurbach GD, Tomkins GM (1968) Tyrosine amino transferase enzyme induction independent of adenosine 3′,5′-monophosphate. Science 162: 1018–1021PubMedCrossRefGoogle Scholar
  9. Hilf R (1973) Biochemical studies of experimental mammary tumors as related to breast cancers. In: Busch H (ed) Methods in cancer research, vol. 7. Academic Press, New York, pp 55–114Google Scholar
  10. Huang FL, Cho-Chung YS (1982) Hormone-regulated expression of cellularras H oncogene in mammary carcinomas in rats. Biochem Biophys Res Commun 107: 411–415PubMedCrossRefGoogle Scholar
  11. Johnson RA, Weldon J (1977) Characteristics of the enzymatic hydrolysis of 5′-adenylamidodiphosphate: implications for the study of adenylate cyclase. Arch Biochem Biophys 183: 216–227PubMedCrossRefGoogle Scholar
  12. Kang Y-H, Sahai A, Criss WE, West WLJ (1982) Ultracytochemical localization of estrogenstimulated guanylate cyclase in rat uterus. Histochem Cytochem 30: 331–342Google Scholar
  13. Klinge CM, Liu DK (1985) DNA polymerases in normal and neoplastic mammary tissues from rats of differing lactational status. Fed Proc 44: 911Google Scholar
  14. Kulick D, Liu DK (1981) Isolation and characterization of polypoid nuclei of R3230AC mammary adenocarcinoma and comparison with normal mammary nuclei. Cancer Res 41: 3907–3912PubMedGoogle Scholar
  15. Liu DK, Williams GH, Fritz PJ (1975) Alkaline ribonuclease and ribonuclease inhibitor in mammary gland during the lactation cycle and in the R3230AC mammary tumor. Biochem J 148: 67–76PubMedGoogle Scholar
  16. Mao CC, Guidotti A, Costa E (1974) The regulation of cyclic guanosine monophosphate in rat cerebellum: possible involvement of putative amino acid neurotransmitters. Brain Res 79: 510–514PubMedCrossRefGoogle Scholar
  17. Matusik RJ, Hilf R (1976) Brief Communication: relationship of adenosine 3′5′-cyclic monophosphate to growth of dimethylbenz[a]anthracene-induced mammary tumors in rats. J Natl Cancer Inst 56: 659–661PubMedGoogle Scholar
  18. McGuire WL, Huff K (1972) Mammary carcinoma: a specific biochemical defect in autonomous tumors. Science 75: 335–336CrossRefGoogle Scholar
  19. Moller PC, Chang JP, Partridge LR (1984) Cytochemical localization of adenyl cyclase in isoproterenol stimulated hepatoma ascites cells. Virchows Arch [Cell Pathol] 47: 47–53CrossRefGoogle Scholar
  20. Murad F, Arnold WP, Mittal CK, Braughler JM (1979) Properties and regulation of guanylate cyclase and some proposed functions for cyclic AMP. Adv Cyclic Nucleotide Res 11: 175–204PubMedGoogle Scholar
  21. Orloski JM, Fritz PJ, Liu DK (1980) Ribonuclease H activity in rat mammary gland during the lactation cycle and in R3230AC mammary adenocarcinoma. Biochim Biophys Acta 632: 1–10PubMedGoogle Scholar
  22. Orloski JM, Fritz PJ, Liu DK (1982) Pregnancy stimulates DNA synthesis in R3230AC mammary adenocarcinoma. Eur J Cancer Clin Oncol 18: 99–106PubMedCrossRefGoogle Scholar
  23. Pascolini R, Vaghetti D, Spreca A, Marinelli M, Lorvik S (1983) Cytochemical study on the distribution of adenylate cyclase in guinea pig testis. Anat Rec 207: 629–633PubMedCrossRefGoogle Scholar
  24. Pastan I, Johnson GS, Anderson WB (1975) Role of cyclic nucleotides in growth control. Ann Rev Biochem 44: 491–522PubMedCrossRefGoogle Scholar
  25. Poeggel G, Luppa H, Bernstein G, Weiss J (1984) Histochemistry of adenylate cyclase. Int Rev Cycol 89: 35–64Google Scholar
  26. Reik L, Petgold GL, Higgins PG, Barrnet RJ (1970) Hormone sensitive adenyl cyclase: cytochemical localization in rat liver. Science 168: 382–384PubMedCrossRefGoogle Scholar
  27. Rillema JA (1975) Cyclic nucleotides and the effect of prolactin on uridine incorporation into RNA in mammary gland expiants of mice. Horm Metab Res 7: 45–49CrossRefGoogle Scholar
  28. Russo J, Wells PA, Russo IHA (1977) Adenosine triphoshatases as histochemical markers for the cell of origin in experimental mammary carcinoma. Canc Res 37: 1088–1098Google Scholar
  29. Ryan WL, Heidrick ML (1974) Role of cyclic nucleotides in cancer. Adv Cyclic Nucleotide Res 4: 81–116PubMedGoogle Scholar
  30. Sapag-Hagar M, Greenbaum AL (1974) The role of cyclic nucleotides in the development and function of rat mammary tissue. FEBS Lett 46: 180–183PubMedCrossRefGoogle Scholar
  31. Schultze W, Krause EG (1983) Cytochemical demonstration of guanylate cyclase activity in cardiac muscle. Histochemistry 77: 243–254CrossRefGoogle Scholar
  32. Thomas EW, Murad F, Looney WB, Morris HP (1973) Adenosine 3′,5′-monophosphatase and guanosine 3′,5′-monophosphate: concentrations in Morris hepatomas of different growth rates. Biochim Biophys Acta 297: 564–567PubMedGoogle Scholar
  33. Whittliff JL, Gardner DG, Battema WL, Gilbert PJ (1972) Specific estrogen-receptors in the neoplastic and lactating mammary gland of the rat. Biochem Biophys Res Comm 48: 119–125CrossRefGoogle Scholar
  34. Wooding FBP (1977) Comparative mammary fine structure. Symp Zool Soc [Lond] 41: 1–41Google Scholar
  35. Zajic G, Schacht J (1983) Cytochemical demonstration of adenylate cyclase with strontium chloride in the rat pancreas. J Histochem Cytochem 31: 25–28PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Bang H. Hwang
    • 1
  • Dai Kee Liu
    • 1
  1. 1.Departments of Anatomy and Pharmacology, College of MedicineThe Pennsylvania State UniversityHersheyUSA

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