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Breast Cancer Research and Treatment

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01.08.2007 | Review Paper

The role of ATM in breast cancer development

verfasst von: Jana Prokopcova, Zdenek Kleibl, Claire M. Banwell, Petr Pohlreich

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2007

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Abstract

Complete or partial inability to sense and repair DNA damage increases the risk of developing cancer. The ataxia telangiectasia mutated (ATM) protein kinase has a crucial role in response to DNA double-strand breaks. Hereditary mutations in the ATM gene are the cause of a rare genomic instability syndrome ataxia telangiectasia (AT) characterized, among others, by elevated cancer risk. Although clear in homozygotes, numerous studies have failed to find a link between heterozygotes and cancer. However, there is increasing evidence that ATM heterozygotes have an increased risk of developing breast cancer. First, epidemiological studies conferred an increased risk of breast cancer among AT relatives. Second, in vitro studies of heterozygous cells provide strong evidence of hyperradiosensitivity. Third, some clinical studies found an increased frequency of ATM mutations among high-risk breast cancer families.

Swift M, Morrell D, Cromartie E, Chamberlin AR, Skolnick MH, Bishop DT (1986) The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet 39:573–583PubMed

Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G (1995) The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum Mol Genet 4:2025–2032PubMedCrossRef

Concannon P, Gatti RA (1997) Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat 10:100–107PubMedCrossRef

Stankovic T, Kidd AM, Sutcliffe A, McGuire GM, Robinson P, Weber P, Bedenham T, Bradwell AR, Easton DF, Lennox GG, Haites N, Byrd PJ, Taylor AM (1998) ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet 62:334–345PubMedCrossRef

Teraoka SN, Telatar M, Becker-Catania S, Liang T, Onengut S, Tolun A, Chessa L, Sanal O, Bernatowska E, Gatti RA, Concannon P (1999) Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. Am J Hum Genet 64:1617–1631PubMedCrossRef

Sandoval N, Platzer M, Rosenthal A, Dork T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D (1999) Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum Mol Genet 8:69–79PubMedCrossRef

Gatti RA, Tward A, Concannon P (1999) Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. Mol Genet Metab 68:419–423PubMedCrossRef

Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K (1988) Localization of an ataxia-telangiectasia gene to chromosome 11q22–23. Nature 336:577–580PubMedCrossRef

Uziel T, Savitsky K, Platzer M, Ziv Y, Helbitz T, Nehls M, Boehm T, Rosenthal A, Shiloh Y, Rotman G (1996) Genomic organization of the ATM gene. Genomics 33:317–320PubMedCrossRef

10.

Shafman T, Khanna KK, Kedar P, Spring K, Kozlov S, Yen T, Hobson K, Gatei M, Zhang N, Watters D, Egerton M, Shiloh Y, Kharbanda S, Kufe D, Lavin MF (1997) Interaction between ATM protein and c-Abl in response to DNA damage. Nature 387:520–523PubMedCrossRef

11.

Khanna KK (2000) Cancer risk and the ATM gene: a continuing debate. J Natl Cancer Inst 92:795–802PubMedCrossRef

12.

Lakin ND, Weber P, Stankovic T, Rottinghaus ST, Taylor AM, Jackson SP (1996) Analysis of the ATM protein in wild-type and ataxia telangiectasia cells. Oncogene 13:2707–2716PubMed

13.

Rotman G, Shiloh Y (1997) Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? Bioessays 19:911–917PubMedCrossRef

14.

Lim DS, Kirsch DG, Canman CE, Ahn JH, Ziv Y, Newman LS, Darnell RB, Shiloh Y, Kastan MB (1998) ATM binds to beta-adaptin in cytoplasmic vesicles. Proc Natl Acad Sci USA 95:10146–10151PubMedCrossRef

15.

Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506PubMedCrossRef

16.

Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276:42462–42467PubMedCrossRef

17.

Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677PubMedCrossRef

18.

Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D (1999) Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci USA 96:14973–14977PubMedCrossRef

19.

Chen G, Yuan SS, Liu W, Xu Y, Trujillo K, Song B, Cong F, Goff SP, Wu Y, Arlinghaus R, Baltimore D, Gasser PJ, Park MS, Sung P, Lee EY (1999) Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem 274:12748–12752PubMedCrossRef

20.

Wang H, Guan J, Wang H, Perrault AR, Wang Y, Iliakis G (2001) Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase. Cancer Res 61:8554–8563PubMed

21.

Foray N, Marot D, Gabriel A, Randrianarison V, Carr AM, Perricaudet M, Ashworth A, Jeggo P (2003) A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J 22:2860–2871PubMedCrossRef

22.

Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11–Rad50–Nbs1 complex. Science 308:551–554PubMedCrossRef

23.

Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304:93–96PubMedCrossRef

24.

Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR III, Hays L, Morgan WF, Petrini JH (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93:477–486PubMedCrossRef

25.

Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA (2001) Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 105:473–485PubMedCrossRef

26.

Taylor AM, Groom A, Byrd PJ (2004) Ataxia-telangiectasia-like disorder (ATLD)—its clinical presentation and molecular basis. DNA Repair (Amst) 3:1219–1225CrossRef

27.

Cortez D, Wang Y, Qin J, Elledge SJ (1999) Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286:1162–1166PubMedCrossRef

28.

Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406:210–215PubMedCrossRef

29.

Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D’Andrea AD (2002) Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell 109:459–472PubMedCrossRef

30.

Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–429PubMedCrossRef

31.

Falck J, Mailand N, Syljuasen RG, Bartek J, Lukas J (2001) The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410:842–847PubMedCrossRef

32.

Gatei M, Sloper K, Sorensen C, Syljuasen R, Falck J, Hobson K, Savage K, Lukas J, Zhou BB, Bartek J, Khanna KK (2003) Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem 278:14806–14811PubMedCrossRef

33.

Pommier Y, Sordet O, Rao VA, Zhang H, Kohn KW (2005) Targeting chk2 kinase: molecular interaction maps and therapeutic rationale. Curr Pharm Des 11:2855–2872PubMedCrossRef

34.

Falck J, Petrini JH, Williams BR, Lukas J, Bartek J (2002) The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat Genet 30:290–294PubMedCrossRef

35.

Formichi P, Battisti C, Tripodi SA, Tosi P, Federico A (2000) Apoptotic response and cell cycle transition in ataxia telangiectasia cells exposed to oxidative stress. Life Sci 66:1893–1903PubMedCrossRef

36.

Gladdy RA, Nutter LM, Kunath T, Danska JS, Guidos CJ (2006) p53-independent apoptosis disrupts early organogenesis in embryos lacking both ataxia-telangiectasia mutated and Prkdc. Mol Cancer Res 4:311–318PubMedCrossRef

37.

Piret B, Schoonbroodt S, Piette J (1999) The ATM protein is required for sustained activation of NF-kappaB following DNA damage. Oncogene 18:2261–2271PubMedCrossRef

38.

Karlseder J, Hoke K, Mirzoeva OK, Bakkenist C, Kastan MB, Petrini JH, de Lange T (2004) The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol 2:E240PubMedCrossRef

39.

Morrell D, Cromartie E, Swift M (1986) Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst 77:89–92PubMed

40.

Gumy-Pause F, Wacker P, Sappino AP (2004) ATM gene and lymphoid malignancies. Leukemia 18:238–242PubMedCrossRef

41.

Su Y, Swift M (2000) Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med 133:770–778PubMed

42.

Inskip HM, Kinlen LJ, Taylor AM, Woods CG, Arlett CF (1999) Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia. Br J Cancer 79:1304–1307PubMedCrossRef

43.

Lantelme E, Turinetto V, Mantovani S, Marchi A, Regazzoni S, Porcedda P, De Marchi M, Giachino C (2003) Analysis of secondary V(D)J rearrangements in mature, peripheral T cells of ataxia-telangiectasia heterozygotes. Lab Invest 83:1467–1475PubMedCrossRef

44.

Angele S, Hall J (2000) The ATM gene and breast cancer: is it really a risk factor? Mutat Res 462:167–178PubMedCrossRef

45.

Nathanson KL, Wooster R, Weber BL (2001) Breast cancer genetics: what we know and what we need. Nat Med 7:552–556PubMedCrossRef

46.

Swift M, Morrell D, Massey RB, Chase CL (1991) Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325:1831–1836PubMedCrossRef

47.

Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, Rutgers EJ, Devilee P, Russell NS, van Leeuwen FE, van’t Veer LJ (2000) ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. Am J Hum Genet 66:494–500PubMedCrossRef

48.

Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF (2005) Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97:813–822PubMedCrossRef

49.

Thorstenson YR, Roxas A, Kroiss R, Jenkins MA, Yu KM, Bachrich T, Muhr D, Wayne TL, Chu G, Davis RW, Wagner TM, Oefner PJ (2003) Contributions of ATM mutations to familial breast and ovarian cancer. Cancer Res 63:3325–3333PubMed

50.

Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N (2006) ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38(8):873–875PubMedCrossRef

51.

Teraoka SN, Malone KE, Doody DR, Suter NM, Ostrander EA, Daling JR, Concannon P (2001) Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. Cancer 92:479–487PubMedCrossRef

52.

Sommer SS, Jiang Z, Feng J, Buzin CH, Zheng J, Longmate J, Jung M, Moulds J, Dritschilo A (2003) ATM missense mutations are frequent in patients with breast cancer. Cancer Genet Cytogenet 145:115–120PubMedCrossRef

53.

FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA (1997) Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 15:307–310PubMedCrossRef

54.

Ramsay J, Birrell G, Lavin M (1998) Testing for mutations of the ataxia telangiectasia gene in radiosensitive breast cancer patients. Radiother Oncol 47:125–128PubMedCrossRef

55.

Dork T, Bendix R, Bremer M, Rades D, Klopper K, Nicke M, Skawran B, Hector A, Yamini P, Steinmann D, Weise S, Stuhrmann M, Karstens JH (2001) Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. Cancer Res 61:7608–7615PubMed

56.

Broeks A, Urbanus JH, de Knijff P, Devilee P, Nicke M, Klopper K, Dork T, Floore AN, van’t Veer LJ (2003) IVS10-6T > G, an ancient ATM germline mutation linked with breast cancer. Hum Mutat 21:521–528PubMedCrossRef

57.

Thompson D, Antoniou AC, Jenkins M, Marsh A, Chen X, Wayne T, Tesoriero A, Milne R, Spurdle A, Thorstenson Y, Southey M, Giles GG, Khanna KK, Sambrook J, Oefner P, Goldgar D, Hopper JL, Easton D, Chenevix-Trench G (2005) Two ATM variants and breast cancer risk. Hum Mutat 25:594–595PubMedCrossRef

58.

Szabo CI, Schutte M, Broeks A, Houwing-Duistermaat JJ, Thorstenson YR, Durocher F, Oldenburg RA, Wasielewski M, Odefrey F, Thompson D, Floore AN, Kraan J, Klijn JG, van den Ouweland AM, Wagner TM, Devilee P, Simard J, van’t Veer LJ, Goldgar DE, Meijers-Heijboer H (2004) Are ATM mutations 7271T→G and IVS10-6T→G really high-risk breast cancer-susceptibility alleles? Cancer Res 64:840–843PubMedCrossRef

59.

Clarke RA, Fang ZH, Marr PJ, Lee CS, Kearsley JH, Papadatos G (2002) ATM induction insufficiency in a radiosensitive breast-cancer patient. Australas Radiol 46:329–335PubMedCrossRef

60.

Weil MM, Kittrell FS, Yu Y, McCarthy M, Zabriskie RC, Ullrich RL (2001) Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. Oncogene 20:4409–4411PubMedCrossRef

61.

Hampton GM, Mannermaa A, Winqvist R, Alavaikko M, Blanco G, Taskinen PJ, Kiviniemi H, Newsham I, Cavenee WK, Evans GA (1994) Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Res 54:4586–4589PubMed

62.

Rio PG, Pernin D, Bay JO, Albuisson E, Kwiatkowski F, De Latour M, Bernard-Gallon DJ, Bignon YJ (1998) Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma. Int J Oncol 13:849–853PubMed

63.

Koike M, Takeuchi S, Park S, Hatta Y, Yokota J, Tsuruoka N, Koeffler HP (1999) Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene. Oncology 56:160–163PubMedCrossRef

64.

Bay JO, Uhrhammer N, Pernin D, Presneau N, Tchirkov A, Vuillaume M, Laplace V, Grancho M, Verrelle P, Hall J, Bignon YJ (1999) High incidence of cancer in a family segregating a mutation of the ATM gene: possible role of ATM heterozygosity in cancer. Hum Mutat 14:485–492PubMedCrossRef

65.

Feng J, Yan J, Chen J, Schlake G, Jiang Z, Buzin CH, Sommer SS, Dritschilo A (2003) Absence of somatic ATM missense mutations in 58 mammary carcinomas. Cancer Genet Cytogenet 145:179–182PubMedCrossRef

66.

Janatova M, Zikan M, Dundr P, Matous B, Pohlreich P (2005) Novel somatic mutations in the BRCA1 gene in sporadic breast tumors. Hum Mutat 25:319PubMedCrossRef

67.

Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian S, Bennett LM, Haugen-Strano A, Swensen J, Miki Y (1994) BRCA1 mutations in primary breast and ovarian carcinomas. Science 266:120–122PubMedCrossRef

68.

Boultwood J (2001) Ataxia telangiectasia gene mutations in leukaemia and lymphoma. J Clin Pathol 54:512–516PubMedCrossRef

69.

Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428PubMedCrossRef

70.

Gao G, Bracken AP, Burkard K, Pasini D, Classon M, Attwooll C, Sagara M, Imai T, Helin K, Zhao J (2003) NPAT expression is regulated by E2F and is essential for cell cycle progression. Mol Cell Biol 23:2821–2833PubMedCrossRef

71.

Kim WJ, Vo QN, Shrivastav M, Lataxes TA, Brown KD (2002) Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene 21:3864–3871PubMedCrossRef

72.

Vo QN, Kim WJ, Cvitanovic L, Boudreau DA, Ginzinger DG, Brown KD (2004) The ATM gene is a target for epigenetic silencing in locally advanced breast cancer. Oncogene 23:9432–9437PubMedCrossRef

Titel: The role of ATM in breast cancer development
verfasst von: Jana Prokopcova
Zdenek Kleibl
Claire M. Banwell
Petr Pohlreich
Publikationsdatum: 01.08.2007
Verlag: Kluwer Academic Publishers-Plenum Publishers
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2007
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-006-9406-6

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