Analysis of Proto-oncogene Expression During Liver Regeneration and Hepatocarcinogenesis

  • Nelson Fausto
  • Peter R. Shank


The discovery and characterization of viral oncogenes and the cellular genes from which they originated (cellular or proto-oncogenes) represents one of the most dramatic advances in the field of cancer research in recent years. Elucidation of the role of these genes in the process of oncogenesis and the role of the proto-oncogenes in the control of normal cellular growth and/or differentiation has united the fields of cancer research and cell biology. Despite the vast amount of information which has become available recently on the molecular nature of the alterations which lead to the “activation” of protooncogenes, the precise role of these genes in the development of natural tumors remains to be established. Some investigators have gone so far as to state that “there is as yet no convincing evidence that activated proto-oncogenes are even necessary, much less sufficient for carcinogenesis” [1]. Although this rather extreme view is a minority opinion, it is important to remember that in the complex process encompassing the development of a tumor, the oncogene may be but one player with several others remaining to be elucidated. Given this still unsettled picture, it is particularly important to define the role which various proto-oncogenes play in normal cells and tissues.


Liver Regeneration Partial Hepatectomy Nuclear Oncogene Prereplicative Phase Polysomal Poly 
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  1. 1.
    Duesberg PH (1985) Activated proto-oncogenes: sufficient or necessary for cancer? Science 228: 669–677PubMedGoogle Scholar
  2. 2.
    Campisi J, Gray HE, Pardee AB, Dean M, Sonenshein GE (1984) Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell 36:241–247PubMedGoogle Scholar
  3. 3.
    Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos protooncogene. Nature 311:433–438PubMedGoogle Scholar
  4. 4.
    Muller R, Bravo R, Burckhardt J, Curran T (1984) Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 321:716–720Google Scholar
  5. 5.
    Reed JC, Nowell PC, Hoover RG (1985) Regulation of c-myc mRNA levels in normal human lymphocytes by modulators of cell proliferation. Proc Natl Acad Sci USA 82:4221–4224PubMedGoogle Scholar
  6. 6.
    Kaczmarek L, Calabretta B, Baserga R (1985) Expression of cell cycle-dependent genes in phytohemagglutinin-stimulated human lymphocytes. Proc Natl Acad Sci USA 82: 5375–5379PubMedGoogle Scholar
  7. 7.
    Thompson CB, Challoner PB, Neiman PE, Groudine M (1986) Expression of the c-myb proto-oncogene during cellular proliferation. Nature 319:374–380PubMedGoogle Scholar
  8. 8.
    Fausto N, Shank PR (1983) Oncogene expression in liver regeneration and hepatocarcinogenesis. Hepatology 3:1016–1023PubMedGoogle Scholar
  9. 9.
    Thompson NL, Mead JE, Braun L, Goyette M, Shank PR, Fausto N (1986) Sequential protooncogene expression during liver regeneration. Cancer Res 46:3111–3117PubMedGoogle Scholar
  10. 10.
    Weinberg RA (1985) The action of oncogenes in the cytoplasm and nucleus. Science 230: 770–776PubMedGoogle Scholar
  11. 11.
    Bishop JM (1983) Cellular oncogenes and retroviruses. Ann Rev Biochem 52:301–354PubMedGoogle Scholar
  12. 12.
    Oren M (1985) The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochem Biophys Acta 823:67–78PubMedGoogle Scholar
  13. 13.
    Land H, Parada LF, Weinberg RA (1983) Cellular oncogenes and multistep carcinogenesis. Science 222:771–778PubMedGoogle Scholar
  14. 14.
    Spandidos DA, Wilkie NM (1984) Malignant transformation of early passage rodent cells by a single mutated human oncogene. Nature 310: 469–475PubMedGoogle Scholar
  15. 15.
    Muschel RJ, Williams JE, Lowy DR, Liotta LA (1985) Harvey ras induction of metastatic potential depends upon oncogene activation and the type of recipient cell. Am J Pathol 121:1–8PubMedGoogle Scholar
  16. 16.
    Hayward SW, Neel BG, Astrin SM (1981) Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature (London) 290:475–480Google Scholar
  17. 17.
    Leder P, Battey J, Lenoir G, Moulding C, Murphy W, Potter H, Stewart T, Taub R (1983) Translocations among antibody genes in human cancer. Science 222:765–771PubMedGoogle Scholar
  18. 18.
    Collins S, Groudine M (1982) Amplification of endogenous myc-related DNA sequences in a human myeloid leukemia cell line. Nature 298: 679–681PubMedGoogle Scholar
  19. 19.
    Scolnick EM (1981) Transformation by ratderived oncogenic retroviruses. Microbiol Revs 45:1–8Google Scholar
  20. 20.
    Shimizu K, Goldfarb M, Perucho M, Wigler M (1983) Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. Proc Natl Acad Sci USA 80:383–387PubMedGoogle Scholar
  21. 21.
    Roussel M, Saule S, Langrou C, Rommens C, Beug H, Graff T, Stehelin D (1979) Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature 281:452–455PubMedGoogle Scholar
  22. 22.
    Schwab M, Alitalo K, Klempnauer K-H, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J (1983) Amplified DNA with limited homology to myc is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature (London) 305:245–248Google Scholar
  23. 23.
    Ralston R, Bishop JM (1983) The protein products of the myc and myb oncogenes and adeno-virus Ela are structurally related. Nature 306: 803–806PubMedGoogle Scholar
  24. 24.
    Toda T, Uno I, Ishikawa T, Powers S, Kataoka T, Broek D, Cameron S, Broach J, Matsumoto K, Wigler M (1985) In yeast, ras proteins are controlling elements of adenylate cyclase. Cell 40:27–36PubMedGoogle Scholar
  25. 25.
    Beckner SK, Hattori S, Shih TY (1985) The ras oncogene product p21 is not a regulatory component of adenylate cyclase. Nature 317:71–72PubMedGoogle Scholar
  26. 26.
    Birchmeier C, Broek D, Wigler M (1985) ras proteins can induce meiosis in xenopus oocytes. Cell 43:615–621PubMedGoogle Scholar
  27. 27.
    Armelin HA, Armelin MCS, Kelly K, Stewart T, Leder P, Cochran BH, Stiles CD (1984) Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature. 310:655–660PubMedGoogle Scholar
  28. 28.
    Kaczmarek L, Hyland JK, Watt R, Rosenberg M, Baserga R (1985) Microinjected c-myc as a competence factor. Science 228:1313–1315PubMedGoogle Scholar
  29. 29.
    Thompson CB, Challoner PB, Neiman PE, Groudine M (1985) Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. Nature. 314:363–366PubMedGoogle Scholar
  30. 30.
    Hann SR, Thompson CB, Eisenman RN (1985) c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. Nature. 314:366–369PubMedGoogle Scholar
  31. 31.
    Fausto N (1984) Messenger RNA in regenerating liver: implications for the understanding of regulated growth. Mol Cell Biochem 59:131–147PubMedGoogle Scholar
  32. 32.
    Scholia CA, Tedeschi MV, Fausto N (1980) Gene expression and the diversity of polysomal messenger RNA sequences in regenerating liver. J Biol Chem 255:2855–2860Google Scholar
  33. 33.
    Fausto N, Schultz-Ellison G, Atryzek V, Goyette M (1982) Distribution and specificity of sequences in polyadenylated nuclear RNA of normal, regenerating and neoplastic liver. J Biol Chem 257:2200–2206PubMedGoogle Scholar
  34. 34.
    Savage MJ, Sala-Trepat JM, Bonner J (1978) Measurement of the complexity and diversity of poly (adenylic acid) containing messenger RNA from rat liver. Biochemistry 17:462–467PubMedGoogle Scholar
  35. 35.
    Sippel AE, Hynes N, Groner B, Schutz G (1977) Frequency distribution of messenger sequences within polysomal mRNA and nuclear RNA from rat liver. Eur J Biochem 77:141–151PubMedGoogle Scholar
  36. 36.
    Jacobs H, Birnie GD (1980) Post-transcriptional regulation of messenger abundance in rat liver and hepatoma. Nucleic Acids Res 14: 3087–3103Google Scholar
  37. 37.
    Powell DJ, Friedman JM, Oulette AJ, Krauter KS, Darnell JE Jr (1984) Transcriptional and post-transcriptional control of specific messenger RNAs in adult and embryonic liver. J Mol Biol 179:21–35PubMedGoogle Scholar
  38. 38.
    Glazer RI (1977) The action of N-hydroxy-2-acetylamino-fluorene on the synthesis of ribosomal and poly(A)-RNA in normal and regenerating liver. Biochem Biophys Acta 475:492–500PubMedGoogle Scholar
  39. 39.
    Walker PR, Whitfield JF (1981) Regulation of the prereplicative changes in the synthesis and transport of messenger and ribosomal RNA in regenerating livers of normal and hypocalcemic rats. J Cell Physiol 108:427–437PubMedGoogle Scholar
  40. 40.
    Atryzek V, Fausto N (1979) Accumulation of polyadenylated mRNA during liver regeneration. Biochemistry 18:1281–1287PubMedGoogle Scholar
  41. 41.
    Tedeschi MV, Colbert DA, Fausto N (1978) Transcription of the non-repetitive genome in liver hypertrophy and the homology between nuclear RNA of normal and 12h-regenerating liver. Biochem Biophys Acta 521: 641–649PubMedGoogle Scholar
  42. 42.
    Fausto N, Colbert DA, Greene RF, Tedeschi M (1976) Transcriptional activity and gene expression during liver regeneration. In: Fishman WH, Sell S (eds) Onco-developmental gene expression. Academic Press, New York, pp 35–45Google Scholar
  43. 43.
    Wilkes PR, Birnie GD, Paul J (1979) Changes in nuclear and polysomal polyadenylated RNA sequences during rat liver regeneration. Nucleic Acids Res 6:2193–2208PubMedGoogle Scholar
  44. 44.
    Grady LJ, Campbell WP, North AB (1979) Nonrepetitive DNA transcription in normal and regenerating rat liver. Nucleic Acids Res 7:259–269PubMedGoogle Scholar
  45. 45.
    Grady LJ, Campbell WP, North AB (1981) Sequence diversity of nuclear and polysomal polyadenylated and non-polyadenylated RNA in normal and regenerating rat liver. Eur J Biochem 115:241–245PubMedGoogle Scholar
  46. 46.
    Huber BE, Heilman CA, Wirth PJ, Miller MJ, Thorgeirsson SS (1986) Studies in gene transcription and translation in regenerating rat liver. Hepatology. 6:209–219PubMedGoogle Scholar
  47. 47.
    Spector DH, Varmus HE, Bishop JM (1978) Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates. Proc Natl Acad Sci USA 75:4102–4106PubMedGoogle Scholar
  48. 48.
    Goyette M, Petropoulos CJ, Shank PR, Fausto N (1983) Expression of a cellular oncogene during liver regeneration. Science 219: 510–512PubMedGoogle Scholar
  49. 49.
    Goyette M, Petropoulos CJ, Shank PR, Fausto N (1984) Regulated transcription of c-Ki-ras and c-myc during compensatory growth of rat liver. Mol Cell Biol 4:1493–1498PubMedGoogle Scholar
  50. 50.
    Makino R, Hayashi K, Sugimura T (1984) C-myc transcript is induced in rat liver at very early stage of regeneration or by cycloheximide treatment. Nature 310:697–698PubMedGoogle Scholar
  51. 51.
    Dani CH, Blanchard JM, Piechaczyk MS, El Sabouty S, Marty L, Janteur PH (1984) Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 81:7046–7050PubMedGoogle Scholar
  52. 52.
    Kelly K, Cochran BH, Stiles CD, Leder P (1983) Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610PubMedGoogle Scholar
  53. 53.
    Grisham J (1962) Morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver: autoradiography with thymidine H3. Cancer Res 22: 842–849PubMedGoogle Scholar
  54. 54.
    Bucher NLR, Malt RA (1971) Regeneration of liver and kidney. Little Brown, Boston, pp 1–176Google Scholar
  55. 55.
    Bouwens L, Baekeland M, Wisse E (1984) Importance of local proliferation in the expanding Kupffer cell population of rat liver after zymosan stimulation and partial hepatectomy. Hepatology 4:213–219PubMedGoogle Scholar
  56. 56.
    Rabbits PH, Watson JV, Lamond A, Forster A, Stinson MA, Evan G, Fischer W, Atherton E, Sheppard R, Rabbits TH (1985) Metabolism of c-myc gene products: c-myc mRNA and protein expression in the cell cycle. EMBO J 4:2009–2015Google Scholar
  57. 57.
    Corral M, Tichonicky L, Guguen-Guillouzo C, Corcos D, Raymondjean M, Paris B, Kruh J, Defer N (1985) Expression of c-fos oncogene during hepatocarcinogenesis, liver regeneration and in synchronized HTC cells. Exptl Cell Res 160:427–434PubMedGoogle Scholar
  58. 58.
    Reich NC, Levine AJ (1984) Growth regulation of a cellular tumor antigen, p53, in nontransformed cells. Nature 308:199–201PubMedGoogle Scholar
  59. 59.
    Mercer WE, Baserga R (1985) Expression of the p53 protein during the cell cycle of human peripheral blood lymphocytes. Exptl Cell Res 160: 31–46PubMedGoogle Scholar
  60. 60.
    Mercer WE, Nelson D, DeLeo L, Old LJ, Baserga R (1982) Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc Natl Acad Sci USA 79:6309–6312PubMedGoogle Scholar
  61. 61.
    Kaczmarek L, Oren M, Baserga R (1986) Cooperation between the p53 protein tumor antigen and platelet-poor plasma in the induction of cellular DNA synthesis. Exptl Cell Res 161:268–272Google Scholar
  62. 62.
    Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH (1982) Mechanisms of activation of a human oncogene. Nature 300: 143–149PubMedGoogle Scholar
  63. 63.
    Furth ME, Davis LJ, Fleurdelys B, Scolnick EM (1982) Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol 43:294–304PubMedGoogle Scholar
  64. 64.
    McGowan JA, Atryzek V, Fausto N (1979) Effects of protein-deprivation on the regeneration of rat after partial hepatectomy. Biochem J 180:25–35PubMedGoogle Scholar
  65. 65.
    Russell WE, Bucher NLR (1983) Vasopressin modulates liver regeneration in the Brattleboro rat. Am J Physiol 245: 321–324Google Scholar
  66. 66.
    Cruise JL, Houck K, Michalopoulos GK (1985) Induction of DNA synthesis in cultured rat hepatocytes through stimulation of α′ adrenoreceptor by norepinephrine. Science 277:749–751Google Scholar
  67. 67.
    Bucher NLR, Patel U, Cohen S (1978) Hormonal factors concerned with liver regeneration. In: Hepatotrophic factors. Ciba Foundation Symp 55. Elsevier, Amsterdam, pp 95–107Google Scholar
  68. 68.
    Richman RA, Clause TH, Pilkis SJ, Friedman DL (1976) Hormonal stimulation of DNA synthesis in primary cultures of rat hepatocytes. Proc Natl Acad Sci USA 73:3589–3593PubMedGoogle Scholar
  69. 69.
    Leffert HL, Koch KS (1978) Proliferation of hepatocytes. In: Hepatotrophic factors. Ciba Foundation Symp 55. Elsevier, Amsterdam, pp 61–82Google Scholar
  70. 70.
    McGowan JA, Strain AJ, Bucher NRL (1981) DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon and cyclic AMP. J Cell Physiol 108:353–363PubMedGoogle Scholar
  71. 71.
    Pledger WJ, Stiles CD, Antoniades HN, Sher CD (1977) Induction of DNA synthesis in BALB/ c3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci USA 74:4481–4485PubMedGoogle Scholar
  72. 72.
    Earp HS, O’Keefe EJ (1981) Epidermal growth factor receptor number decreases during rat liver regeneration. J Clin Invest 67:1580–1583PubMedGoogle Scholar
  73. 73.
    Francavilla A, Ove P, Polimeno L, Sciascia C, Coetzee ML, Starzl TE (1986) Epidermal growth factor and proliferation in rat hepatocytes in primary culture isolated at different times after partial hepatectomy. Cancer Res 46:1318–1323PubMedGoogle Scholar
  74. 74.
    Soares MB, Ishii DN, Efstratiadis A (1985) Developmental and tissue-specific expression of a family of transcripts related to rat insulin-like growth factor II mRNA. Nucleic Acids Res 13:1119–1134PubMedGoogle Scholar
  75. 75.
    Rechler MM, Eisen HJ, Higa OZ, Nissley SP, Moses AC, Schilling EE, Fenoy I, Bruni CB, Phillips LS, Baird KL (1979) Characterization of a somatomedin (insulin-like growth factor) synthesized by fetal rat liver organ cultures. J Biol Chem 254: 7942–7950PubMedGoogle Scholar
  76. 76.
    Nakamura T, Tomita Y, Hirai R, Yamaoka K, Kaji K, Ichihara A (1985) Inhibitory effect of transforming growth factor β on DNA synthesis of adult rat hepatocytes in primary culture. Biochem Biophys Res Commun 133:1042–1050PubMedGoogle Scholar
  77. 77.
    McMahon JB, Richards WL, del Campo AA, Song MKH, Thorgeirsson SS (1986) Differential effects of transforming growth factor β on proliferation of normal and malignant rat liver epithelial cells in culture. Cancer Res 46:4665–4671PubMedGoogle Scholar
  78. 78.
    Sporn MB, Roberts AB (1985) Autocrine growth factors and cancer. Nature 313: 745–747PubMedGoogle Scholar
  79. 79.
    Goustin AS, Leof EB, Shipley GD, Moses HL (1986) Growth factors and cancer. Cancer Res 46:1015–1029PubMedGoogle Scholar
  80. 80.
    Yaswen P, Goyette M, Shank PR, Fausto N (1985) Expression of c-Ki-ras, c-Ha-ras and c-myc in specific cell types during hepatocarcinogenesis. Mol Cell Biol 5:780–786PubMedGoogle Scholar
  81. 81.
    Makino R, Hayashi K, Sato S, Sugimura T (1984) Expression of the c-Ha-ras and c-myc genes in rat liver tumors. Biochem Biophys Res Commun 119:1096–1102Google Scholar
  82. 82.
    Cote GJ, Lastra BA, Cook JR, Huang DP, Chiu JF (1985) Oncogene expression in rat hepatomas and during hepatocarcinogenesis. Cancer Lett 26:121–127PubMedGoogle Scholar
  83. 83.
    Corcos D, Defer N, Raymondjean M, Paris B, Corral M, Tichonicky L, Kruh J (1984) Correlated increase of the expression of the c-ras genes in chemically induced hepatocarcinomas. Biochem Biophys Res Commun 122:259–264PubMedGoogle Scholar
  84. 84.
    Slamon DJ, deKernion JB, Verma IM, Cline MJ (1984) Expression of cellular oncogenes in human malignancies. Science 224:256–262PubMedGoogle Scholar
  85. 85.
    Jagirdar J. Nonomura A, Patil J, Paronetto F (1985) Activated ras oncogene p21 expression in hepatocellular carcinoma (HCC) and HBsAg-positive liver cells. Hepatology 5:1055 (Abst.)Google Scholar
  86. 86.
    Thor A, Horand Hand P, Wunderlich D, Caruso A, Muraro R, Schlom J (1985) Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. Nature 311:562–565Google Scholar
  87. 87.
    Spandidos DA, Kerr IB (1984) Elevated expression of the human ras oncogene family in premalignant and malignant tumors of the colorectum. Br J Cancer 49:681–688PubMedGoogle Scholar
  88. 88.
    Balmain A, Ramsden M, Bowden GT, Smith J (1984) Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papil-lomas. Nature 307:658–660PubMedGoogle Scholar
  89. 89.
    Schwab M, Ellison J, Busch M, Rosenau W, Varmus HE, Bishop JM (1984) Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc Natl Acad Sci USA 81:4940–4944PubMedGoogle Scholar
  90. 90.
    Huber BE, Dearfield KL, Williams JR, Heilman CA, Thorgeirsson SS (1985) Tumorigenicity and transcriptional modulation of c-myc and N-ras oncogenes in a human hepatoma cell line. Cancer Res 45:4322–4329PubMedGoogle Scholar
  91. 91.
    Yaswen P, Hayner NT, Fausto N (1984) Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers. Cancer Res 44:324–331PubMedGoogle Scholar
  92. 92.
    Braun L, Goyette M, Yaswen P, Thompson NL, Fausto N (1987) Liver epithelial cells from carcinogen treated rats: Growth in culture and tumorigenicity after transfection with the ras oncogene. Cancer Res (in press)Google Scholar
  93. 93.
    Beer DG, Schwarz M, Swada N, Pitot HC (1986) Expression of H-ras and c-myc proto-oncogenes in isolated γ-glutamyl transpeptidase-positive rat hepatocytes and in hepatocellular carcinomas induced by diethylnitrosamine. Cancer Res 46: 2435–2441PubMedGoogle Scholar
  94. 94.
    Notario V, Sukumar S, Santos E, Barbacid M (1984) A common mechanism for the malignant activation of ras oncogenes in human neoplasia and in chemically induced animal tumors. In: Vande Woude GF, Levine AJ, Topp WC, Watson JD (eds) Cancer Cells: II. Oncogenes and viral genes. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 425–432Google Scholar
  95. 95.
    Sukumar S, Notario V, Martin-Zanca D, Barbacid M (1983) Induction of mammary carcinomas in rats by nitroso-methyl-urea involves the malignant activation of the H-ras-1 locus by single point mutations. Nature 306:658–661PubMedGoogle Scholar
  96. 96.
    Eva A, Aaronson SA (1983) Frequent activation of c-Kis as a transforming gene in fibrosarcomas induced by methylcholanthrene. Science 220: 955–956PubMedGoogle Scholar
  97. 97.
    Balmain A, Pragneil IB (1983) Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303:72–74PubMedGoogle Scholar
  98. 98.
    Guerrero I, Villasante A, Mayer, A, Pellicer A (1984) Carcinogen and radiation-induced mouse lymphomas contain an activated c-ras oncogene. In: Vande Woude GF, Levine AJ, Topp WC, Watson JD (eds) Cancer cells: II. Oncogenes and viral genes. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 455–461Google Scholar
  99. 99.
    Farber E (1984) Cellular biochemistry of the stepwise development of cancer with chemicals. Cancer Res 44: 5463–5474PubMedGoogle Scholar
  100. 100.
    Reynolds SH, Stowers SJ, Maronpot RR, Anderson MW, Aaronson SA (1986) Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse. Proc Natl Acad Sci USA 83: 33–37PubMedGoogle Scholar
  101. 101.
    Zurlo J, Yager J (1985) Oncogene expression during pancreatic regeneration and in chemically induced pancreatic and liver carcinomas in the rat. Fed Proc 44:1493 (Abst).Google Scholar
  102. 102.
    Ishikawa F, Takaku F, Nagao M, Ochiai M, Hayashi K, Takayama S and Sugimura T (1985) Activated oncogenes in a rat hepatocellular carcinoma induced by 2-amino-3-methyl-imidazo [4, 5-f] quinoline. Jpn J Can Res (Gann) 76:425–428Google Scholar
  103. 103.
    Varmus HE (1984) Do hepatitis B viruses make a genetic contribution to primary hepatocellular carcinoma? In: Vyas GN, Dienstag JL, Hoofnagle JH (eds) Viral hepatitis and liver disease. Grune and Stratton, Orlando, pp 411–414Google Scholar
  104. 104.
    Yokota J, Tsunetsugu-Yokota Y, Battifora H, LeFevre C, Cline MJ (1986) Alterations of myc, myb and Ras Ha proto-oncogenes in cancers are frequent and show clinical correlation. Science 231:261–264PubMedGoogle Scholar
  105. 105.
    Garte SJ, Hood AT, Hochwalt AE, D’Eustachio P, Snyder CA, Segal A, Albert RE (1985) Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents. Carcinogenesis 6:1709–1712PubMedGoogle Scholar
  106. 106.
    Tur-Kaspa R, Teicher L, Levine BJ, Skoultchi AI, Shafritz DA (1986) Use of electroporation to introduce biologically active foreign genes into primary rat hepatocytes. Mol Cell Biol 6:716–718PubMedGoogle Scholar

Copyright information

© Springer Japan 1987

Authors and Affiliations

  • Nelson Fausto
    • 1
  • Peter R. Shank
    • 2
  1. 1.Department of Pathology and Laboratory Medicine, Division of Biology and MedicineBrown UniversityProvidenceUSA
  2. 2.Section of Molecular, Cell and Developmental Biology, Division of Biology and MedicineBrown UniversityProvidenceUSA

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