Breast Cancer Research and Treatment

, Volume 44, Issue 1, pp 1–22 | Cite as

Defining a role for c-Myc in breast tumorigenesis

  • Sharyl J. Nass
  • Robert B. Dickson
Article

Abstract

The proto-oncogene c-myc is commonly amplified and overexpressed in human breast tumors, and the tumorigenic potential of c-myc overexpression in mammary tissue has been confirmed by both in vitro and in vivo models of breast cancer. However, the mechanisms by which Myc promotes tumorigenesis are not well understood. Recent evidence indicates that Myc can promote cell proliferation as well as cell death via apoptosis. These studies provide new insight and impetus in defining a role for c-Myc in breast tumorigenesis and may point toward novel targets for breast cancer therapy.

apoptosis cell cycle amplification overexpression breast neoplasia c-Myc 

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References

  1. 1.
    Ryan KM, Birnie GD: Myc oncogenes: the enigmatic family. Biochem J 314:713–721, 1996Google Scholar
  2. 2.
    Marcu KB, Bossone SA, Patel AJ: Myc function and regulation. Annu Rev Biochem 61:809–850, 1992Google Scholar
  3. 3.
    Spencer CA, Groudine M: Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res 56:1–48, 1991Google Scholar
  4. 4.
    Kato GJ, Dang CV: Function of the c-Myc oncoprotein. FASEB J 6:3065–3072, 1992Google Scholar
  5. 5.
    Meichle A, Philipp A, Eilers M: The functions of the Myc proteins. Biochim Biophys Acta 1114:129–146, 1992Google Scholar
  6. 6.
    Roy AL, Carruthers C, Gutjahr R, Roeder RG: Direct role for Myc in transcription initiation mediated by interactions with TFH-I. Nature 365:359–361, 1993Google Scholar
  7. 7.
    Lee LA, Dolde C, Barrett J, Wu CS, Dang CV: A link between c-myc-mediated transcriptional repression and neoplastic transformation. J Clin Invest 97:1687–1695, 1996Google Scholar
  8. 8.
    Amati B, Land H: Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. Curr Opin Genet Dev 4:102–108, 1994Google Scholar
  9. 9.
    Eisenman RN: Myc, Max, and Mad: A regulatory network. Adv Oncol 10:3–6, 1994Google Scholar
  10. 10.
    Hurlin PJ, Queva C, Koskinen P, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN: Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 14:5646–5659, 1995Google Scholar
  11. 11.
    Ayer DE, Lawrence QA, Eisenman RN: Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 80:767–776, 1995Google Scholar
  12. 12.
    Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, Skoultchi AI, DePinho RA: An amino-terminal domain of Mxil mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3. Cell 80:777–786, 1995Google Scholar
  13. 13.
    Hurlin PJ, Foley KP, Ayer DE, Hanahan D, Eisenman RN, Arbeit JA: Regulation of c-Myc and Mad during epidermal differentiation and HPV-associated tumorigenesis. Oncogene 11:2487–2501, 1995Google Scholar
  14. 14.
    Gandarillas A, Watt FW: Changes in expression of members of the fos and jun families and myc network during terminal differentiation of human keratinocytes. Oncogene 11:1403–1407, 1995Google Scholar
  15. 15.
    Larsson LG, Pettersson M, Oberg F, Nilsson K, Luscher B: Expression of mad, mxil, max, and c-myc during induced differentiation of hematopoietic cells: opposite regulation of mad and c-myc. Oncogene 9:1247–1252, 1994Google Scholar
  16. 16.
    Ayer DE, Eisenman RN: A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev 7:2110–2119, 1993Google Scholar
  17. 17.
    Zervos AS, Gyuris J, Brent R: Mxil, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72:223–232, 1993Google Scholar
  18. 18.
    Packham G, Cleveland JL: c-Myc and apoptosis. Biochim Biophys Acta 1242:11–28, 1995Google Scholar
  19. 19.
    Miltenberger RJ, Sukow KA, Farnham PJ: An E-box-mediated increase in cad transcription at the G1/S-phase boundary is suppressed by inhibitory c-Myc mutants. Mol Cell Biol 15:2527–2535, 1995Google Scholar
  20. 20.
    Galaktionov K, Chen X, Beach D: Cdc25 cell-cycle phosphatase as a target of c-myc. Nature 382:511–517, 1996Google Scholar
  21. 21.
    Seth A, Gupta S, Davis RJ: Cell cycle regulation of the c-myc transcriptional activation domain. Mol Cell Biol 13:4125–4136, 1993Google Scholar
  22. 22.
    Adnane J, Robbins PD: The retinoblastoma susceptibility gene product regulates Myc-mediated transcription. Oncogene 10:381–387, 1995Google Scholar
  23. 23.
    Gu W, Bhatia K, Magrath IT, Dang CV, Dalla-Favera R: Binding and suppression of the Myc transcriptional activation domain by p107. Science 264:251–254, 1994Google Scholar
  24. 24.
    Beijersbergen RL, Hijmans EM, Zhu L, Bernards R: Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. EMBO J 13:4080–4086, 1994Google Scholar
  25. 25.
    Meikrantz W, Schlegel R: Apoptosis and the cell cycle. J Cell Biochem 58:160–174, 1995Google Scholar
  26. 26.
    Barone MV, Courtneidge SA: Myc but not fos rescue of PDGF signalling block caused by kinasc-inactive Src. Nature 378:509–512, 1995Google Scholar
  27. 27.
    Eisenman RN, Cooper JA: Beating a path to Myc. Nature 378:438–439, 1995Google Scholar
  28. 28.
    Muthuswamy SK, Muller WJ: Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor. Oncogene 11:271–279, 1995Google Scholar
  29. 29.
    Muthuswamy SK, Siegel PM, Dankort DL, Webster MA, Muller WJ: Mammary tumors expressing the neu proto-oncogene possess elevated c-Src tyrosine kinase activity. Mol Cell Biol 14:735–743, 1994Google Scholar
  30. 30.
    Mudryj M, Hiebert SW, Nevins JN: A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J 9:2179–2184, 1990Google Scholar
  31. 31.
    Roussel MF, Davis JN, Cleveland JL, Ghysdael J, Hiebert SW: Dual control of myc expression through a single DNA binding site targeted by ets family and E2F-1. Oncogene 9:405–415, 1994Google Scholar
  32. 32.
    Riggs KJ, Saleque S, Wong KK, Merrell KT, Lee JS, Shi Y, Calame K: Yin-Yang 1 activates the c-myc promoter. Mol Cell Biol 13:7487–7495, 1993Google Scholar
  33. 33.
    La Rosa FA, Pierce JW, Sonenshein GE: Differential regulation of the c-myc oncogene promotor by the NF-κB rel family of transcription factors. Mol Cell Biol 14:1039–1044, 1994Google Scholar
  34. 34.
    Marti A, Feng Z, Jehn B, Djonov V, Chicaiza G, Altermatt HJ, Jaggi R: Expression and activity of cell cycle regulators during proliferation and programmed cell death in the mammary gland. Cell Death Diff 2:227–283, 1995Google Scholar
  35. 35.
    Strange R, Li F, Saurer S, Burkhardt A, Frilis RR: Apoptotic cell death and tissue remodeling during mouse mammary gland involution. Development 115:49–68, 1992Google Scholar
  36. 36.
    Dubik D, Dembinski TC, Shiu RPC: Stimulation of c-myc oncogene expression associated with estrogen-induced proliteration of human breast cancer cells. Cancer Res 47:6517–6521, 1987Google Scholar
  37. 37.
    van der Burg B, van Selm-Miltenburg AJP, de Laat SW, van Zoelen EJJ: Direct effects of estrogen on c-fos and c-myc protooncogene expression and cellular proliferation in human breast cancer cells. Mol Cell Endo 64:223–228, 1989Google Scholar
  38. 38.
    Wosikowski K, Eppenberger U, Kung W, Nagamine Y, Mueller H: c-fos, c-jun and c-myc expressions are not growth rate limiting for the human MCF-7 breast cancer cells. Biochem Biophys Res Commun 188:1067–1076, 1992Google Scholar
  39. 39.
    Davidson NE, Prestigiacomo LJ, Hahm HA: Induction of jun gene family members by transforming growth factor α but not 17ß-estradiol in human breast cancer cells. Cancer Res 53:291–297, 1993Google Scholar
  40. 40.
    Leygue E, Gol-Winkler R, Gompel A, Louis Sylvestre C, Soquet L, Staub S, Kuttenn F, Mauvais-Jarvis P: Estradiol stimulates c-myc proto-oncogene expression in normal human breast epithelial cells in culture. J Steroid Biochem Molec Biol 52:299–305, 1995Google Scholar
  41. 41.
    Earashi M, Endo Y, Obata T, Minami M, Noguchi M, Miyazaki I, Sasaki T: Effects of linoleic acid and eicosanoid synthesis inhibitors on the growth and c-myc oncogene expression of human breast cancer cells. Int J Oncol 8:145–151, 1996Google Scholar
  42. 42.
    Fernandez-Pol JA, Talkad VD, Klos DJ, Hamilton PD: Suppression of the EGF-dependent induction of c-myc proto-oncogene expression by transforming growth factor beta in a human breast carcinoma cell line. Biochem Biophys Res Commun 144:1197–1205, 1987Google Scholar
  43. 43.
    Wilcken NRC, Sarcevic B, Musgrove EA, Sutherland RL: Differential effects of retinoids and antiestrogens on cell cycle progression and cell cycle regulatory genes in human breast cancer cells. Cell Growth Diff 7:65–74, 1996Google Scholar
  44. 44.
    Vink-van Wijngaarden T, Pols HAP, Buurman CJ, van den Bemd GJCM, Dorssers LCJ, Birkenhager JC, van Leewen JPTM: Inhibition of breast cancer cell growth by combined treatment with vitamin D3 analogues and tamoxifen. Cancer Res 54:5711–5717, 1994Google Scholar
  45. 45.
    Musgrove EA, Hamilton JA, Lee CSL, Sweeney KJE, Watts CKW, Sutherland RL: Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol Cell Biol 13:3577–3587, 1993Google Scholar
  46. 46.
    Musgrove EA, Lee CSL, Sutherland RL: Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor α, epidermal growth factor receptor, c-fos, and c-myc genes. Mol Cell Biol 11:5032–5043, 1991Google Scholar
  47. 47.
    Wong MSJ, Murphy LC: Differential regulation of c-myc by progestins and antiestrogens in T-47D human breast cancer cells. J Steroid Biochem Mol Biol 39:39–44, 1991Google Scholar
  48. 48.
    Le Roy X, Escot C, Brouillet JP, Theillet C, Maudelonde T, Simony-Lafontaine J, Pujol H, Rochefort H: Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer. Oncogene 6:431–437, 1991Google Scholar
  49. 49.
    Eppenberger U, Wosikowski K, Kung W: Pharmacologic and biologic properties of Droloxifene, a new antiestrogen. Am J Clin Oncol 14:S5–S14, 1991Google Scholar
  50. 50.
    Wosikowski K, Kung W, Hasmann M, Loser R, Eppenberger U: Inhibition of growth-factor-activated proliferation by anti-estrogens and effects on early gene expression of MCF-7 cells. Int J Cancer 53:290–297, 1993Google Scholar
  51. 51.
    Dubik D, Shiu RPC: Mechanism of estrogen activation of c-myc oncogene expression. Oncogene 7:1587–1594, 1992Google Scholar
  52. 52.
    Reddel RR, Murphy LC, Hall RE, Sutherland RL: Differential sensitivity of human breast cancer cell lines to the growth-inhibitory effects of tamoxifen. Cancer Res 45:1525–1531, 1985Google Scholar
  53. 53.
    Jaiyesimi IA, Buzdar AU, Decker DA, Hortobagyi GN: Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol 13:513–529, 1995Google Scholar
  54. 54.
    Vignon F, Bouton MM, Rochefort H: Antiestrogens inhibit the mitogenic effect of growth factors on breast cancer cells in the total absence of estrogens. Biochem Biophys Res Commun 146:1502–1508, 1987Google Scholar
  55. 55.
    Kang Y, Cortina R, Perry RR: Role of c-myc in tamoxifen-induced apoptosis in estrogen-independent breast cancer cells. JNCI 88:279–284, 1996Google Scholar
  56. 56.
    Shiu RP, Watson PH, Dubik D: c-myc oncogene expression in estrogen-dependent and-independent breast cancer. Clin Chem 39:353–355, 1993Google Scholar
  57. 57.
    Dubik D, Shiu RPC: Transcriptional regulation of c-myc oncogene expression by estrogen in hormone-responsive human breast cancer cells. J Biol Chem 263:12705–12708, 1988Google Scholar
  58. 58.
    Miller TL, Jin Y, Sun JM, Coutts AS, Murphy LC, Davie JR: Analysis of human breast cancer nuclear proteins binding to the promoter elements of the c-myc gene. J Cell Biochem 60:560–571, 1996Google Scholar
  59. 59.
    Miller TL, Huzel NJ, Davie JR, Murphy LC: C-myc gene chromatin of estrogen receptor positive and negative breast cancer cells. Mol Cell Endocrinol 91:83–89, 1993Google Scholar
  60. 60.
    Watson PH, Pon RT, Shiu RPC: Inhibition of c-myc expression by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer. Cancer Res 51:3996–4000, 1991Google Scholar
  61. 61.
    Thomas TJ, Faaland CA, Gallo MA, Thomas T: Suppression of c-myc oncogene expression by a poly amine-complexed triplex-forming oligonucleotide in MCF-7 breast cancer cells. Nucl Acid Res 23:3594–3599, 1995Google Scholar
  62. 62.
    Ray RB, Steele R, Seftor E, Hendrix M: Human breast carcinoma cells transfected with the gene encoding a c-myc promoter-binding protein (MBP-1) inhibits tumors in nude mice. Cancer Res 55:3747–3751, 1995Google Scholar
  63. 63.
    Fornari FA, Jarvis WD, Grant S, Orr MS, Randolph JK, White FKH, Gewirtz DA: Growth arrest and non-apoptotic cell death associated with the suppression of c-Myc expression in MCF-7 breast tumor cells following acute exposure to doxorubicin. Biochem Pharmacol 51:931–940, 1996Google Scholar
  64. 64.
    Fornari FA, Jarvis WD, Grant S, Orr MS, Randolph JK, White FKH, Mumaw VR, Lovings ET, Freeman RH, Gewirtz DA: Induction of differentiation and growth arrest associated with nascent (nonoligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubicin. Cell Growth Diff 5:723–733, 1994Google Scholar
  65. 65.
    Bunch RT, Povirk LF, Orr MS, Randolph JK, Fornari FA, Gewirtz DA: Influence of amsacrine (m-AMSA) on bulk and gene-specific DNA damage and c-myc expression in MCF-7 breast tumor cells. Biochem Pharmacol 47:317–329, 1994Google Scholar
  66. 66.
    Gewirtz DA, Fornari FA, Orr M, Randolph JK, Povirk L, Bunch RT: Dissociation between bulk damage to DNA and the antiproliferative activity of teniposide (VM-26) in the MCF-7 breast tumor cell line: evidence for induction of gene-specific damage and alterations in gene expression. Cancer Res 53:3547–3554, 1993Google Scholar
  67. 67.
    Orr MS, Fornari FA, Randolph JK, Gewirtz DA: Transcriptional down-regulation of c-myc expression in the MCF-7 breast tumor cell line by the topoisomerase II inhibitor, VM-26. Biochim Biophys Acta 1262:139–145, 1995Google Scholar
  68. 68.
    Levy N, Yonish-Rouach E, Oren M, Kimchi A: Complementation by wild-type p53 of interleukin-6 effects on M1 cells: Induction of cell cycle exit and cooperativity with c-myc suppression. Mol Cell Biol 13:7942–7952, 1993Google Scholar
  69. 69.
    Hoang AT, Lutterbach B, Lewis BC, Yano T, Chou TY, Barrett JF, Raffeld M, Hann SR, Dang, CV: A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Mol Cell Biol 15:4031–4032, 1995Google Scholar
  70. 70.
    Escot C, Theillet C, Lidereau R, Spyratos F, Champeme MH, Gest J, Callahan R: Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. Proc Natl Acad Sci USA 83:4834–4838, 1986Google Scholar
  71. 71.
    Cline MJ, Battifora H, Yokota J: Proto oncogene abnormalities in human breast cancer. Correlation with anatomic features and clinical course of disease. J Clin Oncol 5:999–1006, 1987Google Scholar
  72. 72.
    Varley JM, Swallow JE, Brammar WJ, Whittaker JL, Walker RA: Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene 1:423–430, 1987Google Scholar
  73. 73.
    Bonilla M, Ramirez M, Lopez-Cueto J, Gariglio P: In vivo amplification and rearrangement of c-myc oncogene in human breast tumors. J Natl Cancer Inst 80:665–671, 1988Google Scholar
  74. 74.
    Guerin M, Barrois M, Terrier MJ, Spielmann M, Riou G: Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. Oncogene Res 3:21–31, 1988Google Scholar
  75. 75.
    Adnane J, Gaudray P, Simon MP, Simony-Lafontaine J, Jeanteur P, Theillet C: Proto-oncogene amplification and human breast tumor phenotype. Oncogene 4:1389–1395, 1989Google Scholar
  76. 76.
    Garcia I, Dietrich PY, Aapro M, Vauthier G, Vadas L, Engel F: Genetic alteration of c-myc, c-erbB-2 and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas. Cancer Res 49:6675–6679, 1989Google Scholar
  77. 77.
    Tavassoli M, Quirke P, Farzaneh F, Lock NJ, Mayne LV, Kirkham N: C-erbB-2/c-erbA coamplification indicative of lymph node metastasis, and c-myc amplification of high tumor grade, in human breast carcinoma. Br J Cancer 60:505–510, 1989Google Scholar
  78. 78.
    Tsuda H, Hirahashi S, Shimosato Y, Hirota T, Tsugane S, Yamamoto H, Miyajima N, Toyoshima K, Yamamoto T, Yokota J, Yoshida T, Sakamura H, Terada M, Sugimura T: Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res 49:3104–3108, 1989Google Scholar
  79. 79.
    Zhou DJ, Ahuja H, Cline MJ: Proto-oncogene abnormalitics in human breast cancer: c-erbB-2 amplification does not correlate with recurrence of disease. Oncogene 4:105–108, 1989Google Scholar
  80. 80.
    Brouillet JP, Theillet C, Maudelonde T, Defrenne A, Simony-Lafontaine J, Sertour J, Pujol H, Jeanteur P, Rochefort H: Cathepsin D assay in primary breast cancer and lymph nodes: Relationship with c-myc, c-erb-B-2, and int-2 oncogene amplification and node invasiveness. Eur J Cancer 26:437–441, 1990Google Scholar
  81. 81.
    Munzel P, Marx D, Kochel H, Schauer A, Bock KW: Genomic alterations of the c-myc proto-oncogene in relation to the overexpression of c-erbB2 and Ki-67 in human breast and cervix carcinomas. J Cancer Res Clin Oncol 117:603–607, 1991Google Scholar
  82. 82.
    Berns EMJJ, Klijn JGM, van Puten WLJ, van Staveren IL, Portengen H, Foekens JA: c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res 52:1107–1113, 1992Google Scholar
  83. 83.
    Berns EMJJ, Klijn JGM, van Staveren IL, Portengen H, Noordegraaf E, Foekens JA: Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one thousand human breast tumours: Correlation with steroid receptors. Eur J Cancer 28:697–700, 1992Google Scholar
  84. 84.
    Borg A, Baldetorp B, Ferno M, Olsson H, Sigurdsson H: c-myc is an independent prognostic factor in postmenopausal breast cancer. Int J Cancer 51:687–691, 1992Google Scholar
  85. 85.
    Krcipe H, Fischer L, Felgner J, Heidorn K, Mettler L, Parwaresch R: Amplification of c-myc, but not c-erb-B2 is associated with high proliferative capacity in breast cancer. Cancer Res 53:1956–61, 1993Google Scholar
  86. 86.
    Watson PH, Safneck JR Lee K, Dubik D, Shiu RPC: Relationship of c-myc amplification to progression of breast cancer from in situ to invasive tumor and lymph node metastasis. JNCI 85:902–907, 1993Google Scholar
  87. 87.
    Bieche I, Champeme MH, Lidereau R: A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. Cancer Res 54:4274–4276, 1994Google Scholar
  88. 88.
    Contegiacomo A, Pizzi C, Demarchis L, Alimandi M, Delrio P, Dipalma E, Petrella G, Ottini L, French D, Frati L, Bianco AR: High cell kinetics is associated with amplification of the Int-2, Bcl-1, Myc and ErbB-2 proto-oncogenes and loss of heterozygosity at the Df3 locus in primary breast cancers. Int J Cancer 61:1–6, 1995Google Scholar
  89. 89.
    Lonn U, Lonn S, Nilsson B, Stenkvist B: Prognostic value of erb-B2 and myc amplification in breast cancer imprints. Cancer 75:2681–2687, 1995Google Scholar
  90. 90.
    Varley JM, Wainwright AM, Brammar WJ: An unusual alteration in c-myc in tissue from a primary breast carcinoma. Oncogene 1:431–438, 1987Google Scholar
  91. 91.
    Kozbor D, Croce CM: Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. Cancer Res 44:438–441, 1984Google Scholar
  92. 92.
    Callahan R, Campbell G: Mutations in human breast cancer: An overview. JNCI 81:1780–1786, 1989Google Scholar
  93. 93.
    Thor AD, Yandell DW: Molecular pathology of breast carcinoma. In: Harris JR, Lippman ME, Morrow M, Hellman S (eds) Diseases of the Breast. Lippincott-Raven, Philadelphia PA, 1996, pp 221–235Google Scholar
  94. 94.
    Mariani-Costantini R, Escot C, Theillet C, Gentile A, Merlino G, Lidereau R, Callahan R: In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast. Cancer Res 48:199–205, 1988Google Scholar
  95. 95.
    Spandidos DA, Pintzas A, Kakkanas A, Yiagnisis M, Mahera H, Patra E, Agnantis NJ: Elevated expression of the myc gene in human benign and malignant breast lesions compared to normal tissue. Anticancer Res 7:1299–1304, 1987Google Scholar
  96. 96.
    Pavelic ZP, Steele P, Preisler HD: Evaluation of c-myc proto-oncogene in primary human breast carcinomas. Anticancer Res 11:1421–1428, 1991Google Scholar
  97. 97.
    Pavelic ZP, Pavelic K, Carter CP, Pavelic L: Heterogeneity of c-myc expression in histologically similar infiltrating ductal carcinomas of the breast. J Cancer Res Clin Oncol 118:16–22, 1992Google Scholar
  98. 98.
    Pavelic ZP, Pavelic L, Lower EE, Gapany S, Barker EA, Preisler HD: c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and non invasive breast carcinoma. Cancer Res 52:2597–2602, 1992Google Scholar
  99. 99.
    Bland KI, Konstadoulakis MM, Vezeridis MP, Wancbo HJ: Oncogene protein co-expression: Value of Ha-ras, c-myc, c-fos, and p53 as prognostic discriminants for breast carcinoma. Ann Surg 221:706–720, 1995Google Scholar
  100. 100.
    Pietilainen T, Lipponen P, Aaltomaa S, Eskelinen M, Kosma VM, Syrjanen K: Expression of c-myc proteins in breast cancer as related to established prognostic factors and survival. Anticancer Res 15:959–964, 1995Google Scholar
  101. 101.
    Spandidos DA, Field JK, Agnantis NJ, Evan GI, Moore JP: High levels of c-myc protein in human breast tumours determined by a sensitive ELISA technique. Anticancer Res 9:821–826, 1989Google Scholar
  102. 102.
    Mizukami Y, Nonomura A, Takizawa T, Noguchi M, Michigishi T, Nakamura S, Ishizaki T: N-Myc protein expression in human breast carcinoma — Prognostic implications. Anticancer Res 15:2899–2905, 1995Google Scholar
  103. 103.
    Lizard-Nacol S, Lidereau R, Collin F, Arnal M, Hahnel L, Roignot P, Cuisenier J, Guerrin J: Benign breast disease — Absence of genetic alterations at several loci implicated in breast cancer malignancy. Cancer Res 55:4416–4419, 1995Google Scholar
  104. 104.
    Katz E, Carter BJ: A mutant cell line derived from NIH/3T3 cells: two oncogenes required for in vitro transformation. J Natl Cancer Inst 77:909–914, 1986Google Scholar
  105. 105.
    Land H, Parada LF, Weinberg RA: Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304:596–602, 1983Google Scholar
  106. 106.
    Bissonnette RP, Echeverri F, Mahboubi A, Green DR: Apoptotic death induced by c-myc is inhibited by bcl-2. Nature 359:554–556, 1992Google Scholar
  107. 107.
    Fanidi A, Harrington EA, Evan GI: Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature 359:554–556, 1992Google Scholar
  108. 108.
    Strasser A, Harris AW, Bath ML, Cory S: Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348:331–333, 1990Google Scholar
  109. 109.
    Wagner AJ, Small MB, Hay N: Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol Cell Biol 13:2432–2440, 1993Google Scholar
  110. 110.
    Khazaie K, Panayotou G, Aguzzi A, Samarut J, Gazzolo L, Jurdic P: EGF promotes in vivo tumorigenic growth of primary chicken embryo fibroblasts expressing v-myc and enhances in vitro transformation by the v-erbA oncogene. Oncogene 6:21–28, 1991Google Scholar
  111. 111.
    Stern DF, Roberts AB, Roche NS, Sporn MB, Weinberg RA: Differential responsiveness of myc-and ras-transfected cells to growth factors: Selective stimulation of myc-transfected cells by epidermal growth factor. Mol Cell Biol 6:870–877, 1986Google Scholar
  112. 112.
    Sorrentino V, Drozdoff V, McKinney MD, Zeitz L, Fleissner E: Potentiation of growth factor activity by exogenous c-myc expression. Proc Natl Acad Sci USA 83:8167–8171, 1986Google Scholar
  113. 113.
    Leof EB, Proper JA, Moses HL: Modulation of transforming growth factor type β action by activated ras and c-myc. Mol Cell Biol 7:2649–2652, 1987Google Scholar
  114. 114.
    Reiss M, Dibble CL, Narayanan R: Transcriptional activation of the c-myc proto-oncogene in murine keratinocytes enhances the response to epidermal growth factor. J Invest Dermatol 93:136–141, 1989Google Scholar
  115. 115.
    Valverius EM, Ciardiello F, Heldin NE, Blondel B, Merlino G, Smith G, Stampfer MR, Lippman ME, Dickson RB, Salomon DS: Stromal influences on transformation of human mammary epithelial cells overexpressing c-myc and SV40T. J Cell Physiol 145:207–216, 1990Google Scholar
  116. 116.
    Telang NT, Osborne MP, Sweterlitsch LA, Narayanan R: Neoplastic transformation of mouse mammary epithelial cells by deregulated myc expression. Cell Reg 1:863–872, 1990Google Scholar
  117. 117.
    Ball RK, Ziemiecki A, Schonenberger CA, Reichmann E, Redmond SMS, Groner B: V-myc alters the response of a cloned mouse mammary epithelial cell line to lactogenic hormones. Mol Endo 2:133–142, 1988Google Scholar
  118. 118.
    Nguyen HQ, Selvakumaran M, Liebermann DA, Hoffman B: Blocking c-Myc and Max expression inhibits proliferation and induces differentiation of normal and leukemic myeloid cells. Oncogene 11:2439–2444, 1995Google Scholar
  119. 119.
    Schoenenberger CA, Andres AC, Groner B, van der Valk M, Lemeur M, Gerlinger P: Targeted c-myc gene expression in mammary glands of transgenic mice induces mammary tumors with constitutive milk protein gene transcription. EMBO J 7:169–175, 1988Google Scholar
  120. 120.
    Stewart TA, Pattengale PK, Leder P: Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38:627–637, 1984Google Scholar
  121. 121.
    Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P: Consequences of widespread deregulation of the c-myc gene in transgenic mice: Multiple neoplasms and normal development. Cell 45:485–495, 1986Google Scholar
  122. 122.
    Edwards PA, Ward JL, Bradbury JM: Alteration of morphogenesis by the v-myc oncogene in transplants of mammary gland. Oncogene 2:407–412, 1988Google Scholar
  123. 123.
    Amundadottir LT, Johnson MD, Merlino G, Smith G, Dickson RB: Synergistic interaction of transforming growth factor α and c-myc in mouse mammary and salivary gland tumorigenesis. Cell Growth Diff 6:737–748, 1995Google Scholar
  124. 124.
    Sandgren EP, Schroeder JA, Qui TH, Palmiter RD, Brinster RL, Lee DC: Inhibition of mammary gland involution is associated with TGFα-but not c-myc-induced tumorigenesis in transgenic mice. Cancer Res 55:3915–3927, 1995Google Scholar
  125. 125.
    Cardiff RD, Sinn E, Muller W, Leder P: Transgenic oncogenic mice: tumor phenotype predicts genotype. Am J Pathol 139:495–501, 1991Google Scholar
  126. 126.
    Andres AC, van der Valk MA, Schonenberger CA, Fluckiger F, LeMeur M, Gerlinger P, Groner B: Ha-ras and c-myc oncogene expression interferes with morphological and functional differentiation of mammary epithelial cells in single and double transgenic mice. Genes Dev 2:1486–1495, 1988Google Scholar
  127. 127.
    Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P: Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49:465–475, 1987Google Scholar
  128. 128.
    Thompson AM: p53 and breast cancer. The Breast 2:8–10, 1993Google Scholar
  129. 129.
    Wang Y, Ramqvist T, Szekely L, Axelson H, Klein G, Wiman KG: Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line. Cell Growth Differ 4:467–473, 1993Google Scholar
  130. 130.
    Hermeking H, Eick D: Mediation of c-myc-induced apoptosis by p53. Science 265:2091–2093, 1994Google Scholar
  131. 131.
    Wagner AJ, Kokontis JM, Hay N: Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21 waf1/cip1. Genes Dev 8:2817–2830, 1994Google Scholar
  132. 132.
    Saito Y, Ogawa K: Wild type p53 and c-myc cooperation in generating apoptosis of a rat hepatocellular carcinoma cell line (FAA-HTC1). Oncogene 11:1013–1018, 1995Google Scholar
  133. 133.
    Blyth K, Terry A, O'Hara M, Baxter EW, Campbell M, Stewart M, Donehower LA, Onions DE, Neil JC, Cameron ER: Overexpression of a human c-myc transgene and p53 null phenotype in murine thymic lymphomas: contrasting effects of homozygous and heterozygous p53 loss. Oncogene 10:1717–1723, 1995Google Scholar
  134. 134.
    Elson A, Deng C, Campos-Torres J, Donehower LA, Leder P: The MMTV/c-myc transgene and p53 null alleles collaborate to induce T-cell lymphomas, but not mammary carcinomas in transgenic mice. Oncogene 11:181–190, 1995Google Scholar
  135. 135.
    Li M, Hu J, Heermeier K, Hennighausen L, Furth PA: Apoptosis and remodeling of mammary gland tissue during involution proceeds through p53-independent pathways. Cell Growth Diff 7:13–20, 1996Google Scholar
  136. 136.
    Eilers M, Schirm S, Bishop MJ: The Myc protein activates transcription of the alpha-prothymosin gene. EMBO J 10:133–141, 1991Google Scholar
  137. 137.
    Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC: Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119–128, 1992Google Scholar
  138. 138.
    Hanson KD, Shichiri M, Follansbee MR, Sedivy JM: Effects of c-myc expression on cell cycle progression. Mol Cell Biol 14:5748–5755, 1994Google Scholar
  139. 139.
    Karn J, Watson JV, Lowe AD, Green SM, Vedeckis W: Regulation of cell cycle duration by c-myc levels. Oncogene 4:773–787, 1989Google Scholar
  140. 140.
    Heikkila R, Schwab G, Wickstrom E, Loke SL, Pluznik DH, Watt R, Neckers LM: A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1. Nature 328:445–449, 1987Google Scholar
  141. 141.
    Prochownik EV, Kukowska J, Rodgers C: c-myc antisense transcripts accelerate differentiation and inhibit G1 progression in murine crythroleukemia cells. Mol Cell Biol 8:3683–3695, 1988Google Scholar
  142. 142.
    Jansen-Durr P, Meichle A, Steiner P, Pagano M, Finke K, Botz J, Wessbecher J, Draetta G, Eilers M: Differential modulation of cyclin gene expression by MYC. Proc Natl Acad Sci USA 90:3685–368, 1993Google Scholar
  143. 143.
    Philipp A, Schneider A, Vasrik I, Finke K, Xiong Y, Beach D, Alitalo K, Eilers M: Repression of cyclin D1: a novel function of MYC. Mol Cell Biol 14:4032–4043, 1994Google Scholar
  144. 144.
    Hoang AT, Cohen KJ, Barrett JF, Bergstrom DA, Dang CV: Participation of cyclin A in Myc-induced apoptosis. Proc Natl Acad Sci USA 91:6875–6879, 1994Google Scholar
  145. 145.
    Daksis JI, Lu RY, Facchini LM, Marhin WW, Penn LZ: Myc induces cyclin D1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle. Oncogene 9:3635–3645, 1994Google Scholar
  146. 146.
    Roussel MF, Thedoras AM, Pagano M, Sherr CJ: Rescue of defective mitogenic signaling by D-type cyclins. Proc Natl Acad Sci USA 92:6837–6841, 1995Google Scholar
  147. 147.
    Kim YH, Buchholz MA, Chrest FJ, Nordin AA: Up-regulation of c-myc induces the gene expression of the murine homologues of p34cdc2 and cyclin-dependent kinase-2 in T lymphocytes. J Immunol 152:4328–4334, 1994Google Scholar
  148. 148.
    Born TL, Frost JA, Schonthal A, Prendergast GC, Feramisco JR: c-Myc cooperates with activated ras to induce the cdc2 promoter. Mol Cell Biol 14:5710–5718, 1994Google Scholar
  149. 149.
    Steiner P, Philipp A, Lukas J, Godden-Kent D, Pagano M, Mittnacht S, Bartek J, Eilers M: Identification of a Myc-dependent step during the formation of active G1 cyclin-cdk complexes. EMBO J 14: 4814–4826, 1995Google Scholar
  150. 150.
    Nass SJ, Dickson RB: Cell cycle regulation in mammary epithelial cells which overexpress c-myc. AACR Special Conference (Cancer: The Interface Between Basic and Applied Research), Baltimore, MD, 1995, (Abstract #B-27).Google Scholar
  151. 151.
    Stampfer MR, Bartley JC: Human mammary epithelial cells in culture: differentiation and transformation. In: Lippman ME, Dickson RB (eds) Breast Cancer: Cellular and Molecular Biology. Kluwer Academic Publishers, Boston MA, 1988, pp 1–24Google Scholar
  152. 152.
    Nass SJ: Dual effects of c-myc overexpression on the survival and growth of mammary epithelial cells. Ph.D. Thesis, Georgetown University, 1996.Google Scholar
  153. 153.
    Hengst L, Reed SI: Translational control of p27Kip1 accumulation during the cell cycle. Science 271:1861–1864, 1996Google Scholar
  154. 154.
    Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M: Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269:682–685, 1995Google Scholar
  155. 155.
    Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM: Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70:937–948, 1992Google Scholar
  156. 156.
    Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD: Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70:923–935, 1992Google Scholar
  157. 157.
    Chen J, Willingham T, Shuford, Nisen PD: Tumor suppression and inhibition of aneuploid cell accumulation in human brain tumor cells by ectopic overexpression of the cyclin-dependent kinase inhibitor p27KIP1. J Clin Invest 97:1983–1988, 1996Google Scholar
  158. a.157
    Mai S, Fluri M, Siwarski D, Huppi K: Genomic instability in MycER-activated Rat1a cells. Chromosom Res 4:365–371, 1996Google Scholar
  159. 158.
    Canman CE, Kastan MB: Induction of apoptosis by tumor suppressor genes and oncogenes. Sem Cancer Biol 6:17–25, 1995Google Scholar
  160. 159.
    Milner AE, Grand RJA, Waters CM, Gregory CD: Apoptosis in Burkitt lymphoma cells is driven by c-myc. Oncogene 8:3385–3391, 1993Google Scholar
  161. 160.
    Shi Y, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP, Green DR: Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257:212–214, 1992Google Scholar
  162. 161.
    Askew DS, Ashmun RA, Simmons BC, Cleveland JL: Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922, 1991Google Scholar
  163. 162.
    Harrington EA, Bennett MR, Fanidi A, Evan GI: c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J 13:3286–3295, 1994Google Scholar
  164. 163.
    Shi L, Nishioka WK, Th'ng J, Bradbury EM, Litchfield DW, Greenberg AH: Premature p34cdc2 activation required for apoptosis. Science 263:1143–1145, 1994Google Scholar
  165. 164.
    Meikrantz W, Gisselbrecht S, Tam SW, Schlegel R: Activation of cyclin A-dependent protein kinases during apoptosis. Proc Natl Acad Sci USA 91:3754–3758, 1994Google Scholar
  166. 165.
    Rudolph B, Saffrich R, Zwicker J, Henglein B, Muller R, Ansorge W, Eilers M: Activation of cyclin-dependent kinases by Myc mediates induction of cyclin, but not apoptosis. EMBO J 15:3065–3076, 1996Google Scholar
  167. 166.
    Packham G, Porter CW, Cleveland JL: c-Myc induces apoptosis and cell cycle progression by separable, yet overlapping, pathways. Oncogene 13:461–496, 1996Google Scholar
  168. 167.
    Reisman D, Elkind NB, Roy B, Beamon J, Rotter V: c-Myc trans-activates the p53 promotor through a required downstream CACGTG motif. Cell Growth Differ 4:57–65, 1993Google Scholar
  169. 168.
    Miyashita T, Reed JC: Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299, 1995Google Scholar
  170. 169.
    Marin MC, Hsu B, Stephens LC, Brisbay S, McDonnell TJ: The functional basis of c-myc and bcl-2 complementation during multistep lymphomagenesis in vivo. Exp Cell Res 217:240–247, 1995Google Scholar
  171. 170.
    Sakamuro D, Eviner V, Elliott KJ, Showe L, White E, Prendergast GC: c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53-independent mechanisms. Oncogene 11:2411–2418, 1995Google Scholar
  172. 171.
    Hsu B, Marin MC, Elnaggar AK, Stephens LC, Brisbay S, Medonnell TJ: Evidence that c-Myc mediated apoptosis does not require wild-type p53 during lymphomagenesis. Oncogene 11:175–179, 1995Google Scholar
  173. 172.
    Gutierrez MI, Bhatia K, Siwarcki D, Wolff L, Magrath IT, Mushinski JF, Hupp K: Infrequent p53 mutation in mouse tumors with deregulated myc. Cancer Res 52:1032–1035, 1992Google Scholar
  174. 173.
    Lu X, Park SH, Thompson TC, Lane DP: Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation. Cell 70:153–161, 1992Google Scholar
  175. 174.
    Ryan JJ, Prochownik E, Gottlieb CA, Apel IJ, Merino R, Nunez G, Clarke MF: c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. Proc Natl Acad Sci USA 91: 5878–5882, 1994Google Scholar
  176. 175.
    Levine AJ: The tumor suppressor genes. Ann Rev Biochem 62:623–651, 1993Google Scholar
  177. 176.
    Amundadottir LT, Nass SJ, Berchem G, Johnson MD, Dickson RB: Cooperation of TGFα and c-Myc in mouse mammary tumorigenesis: coordinated stimulation of growth and suppression of apoptosis. Oncogene 13:757–765, 1996Google Scholar
  178. 177.
    Nass SJ, Li M, Amundadottir LT, Furth PA, Dickson RB: Role for Bcl-xL in the regulation of apoptosis by EGF and TGFβ1 in c-Myc overexpressing mammary epithelial cells. Biochem Biophys Res Commun 227:248–256, 1996Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Sharyl J. Nass
    • 1
  • Robert B. Dickson
    • 1
  1. 1.Department of Cell Biology and Vincent T. Lombardi Cancer CenterGeorgetown UniversityWashington DCUSA

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