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Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells

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Abstract

Epidemiological studies indicate that there is a positive correlation between alcohol consumption and the risk of breast cancer. Experimental results demonstrate that ethanol is a tumor promoter and chronic ethanol exposure enhances metastasis and growth of breast cancer. The present study used an in vitro model to investigate the molecular mechanism(s) underlying tumor promoting effects of ethanol. With differential display reverse transcription polymerase chain reaction, we demonstrated that human ribosomal large subunit protein L7a (rpL7a) was an ethanol-responsive factor in T47D breast cancer cells. The results of northern blot hybridization revealed that the effect of ethanol on L7a expression was duration- and concentration-dependent. Initial exposure resulted in a 2-fold increase in rpL7a level, whereas a longer exposure period produced a down-regulation. Ethanol had little effect on the stability of rpL7a mRNA; however, the transcription rate of rpL7a was significantly increased by ethanol. Ethanol-induced up-regulation of rpL7a was not a simple stress response, because other stress inducers, such as heat shock, did not affect the expression of rpL7a. Furthermore, breast cancer cells expressed higher level of rpL7a than normal mammary epithelial cells. Ribosomal proteins are known to play an important role in translational regulation, and they have been implicated in the control of cellular transformation, tumor growth, aggressiveness and metastasis. Specially, rpL7a activates the trk oncogene by contributing an amino-terminal-activating sequence to the receptor kinase domain of trk. Thus, ethanol-induced alteration of rpL7a expression may mediate the promoting effects of ethanol on breast cancer development.

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References

  1. Kelsey J, Horn-Ross PL: Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15: 7-16, 1993

    Google Scholar 

  2. Doll R, Peto R: The causes of cancer: quantitative estimates of avoidable risk of cancer in the United States today. J Natl Cancer Inst 66: 1192-1309, 1981

    Google Scholar 

  3. Mufti SI: International society for biomedical research on alcoholism: relationship of cell necrosis and proliferation, free radicals and other agents to alcohol-related cancers. J Cancer Res Clin Oncol 119: 304-305, 1993

    Google Scholar 

  4. Tønnesen H, Møller H, Andersen JR, Jensen E, Juel K: Cancer morbidity in alcohol abusers. British J Cancer 69: 327-332, 1994

    Google Scholar 

  5. Willam RR, Horm JW: Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patient: interview study from Third National Cancer Survey. J Natl Cancer Inst 58: 1298-1305, 1977

    Google Scholar 

  6. Hiatt R: Alcohol consumption and breast cancer. Med Oncol Tumor Pharmacother 7: 143-151, 1990

    Google Scholar 

  7. Plant ML: Alcohol and breast cancer: a review. Intl J Addict 27: 107-128, 1992

    Google Scholar 

  8. Rosenberg L, Metzger LS, Palmer JR: Alcohol consumption and risk of breast cancer: a review of epidemiologic evidence. Epidemiol Rev 15: 133-144, 1993

    Google Scholar 

  9. Longnecker M: Alcohol beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes Control 5: 73-82, 1994

    Google Scholar 

  10. Weiss HA, Brinton LA, Brogan D, Coates RJ, Gammon MD, Malone KE, Schoenberg JB, Swanson CA: Epidemiology of in situ and invasive breast cancer in women aged under 45. British J Cancer 73: 1298-1305, 1996

    Google Scholar 

  11. Bowlin SJ, Leske MC, Varma A, Nasca P, Weinstein A, Caplan L: Breast cancer risk and alcohol consumption: results from a large case-control study. Intl J Epidemiol 26: 915-923, 1997

    Google Scholar 

  12. Swanson CA, Coates RJ, Malone KE, Gammon MD, Schoenberg JB, Brogan DJ, McAdams M, Potischman N, Hoover RN, Brinton LA: Alcohol consumption and breast cancer risk among women under age 45 years. Epidemiol 8: 231-237, 1997

    Google Scholar 

  13. Smith-Warner SA, Spiegelman D, Yaun SS, Vandenbrandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ: Alcohol and breast cancer in women-a pooled analysis of cohort studies. JAMA 279: 535-540, 1998

    Google Scholar 

  14. Vaeth PAC, Schlessinger WA: Alcohol consumption and breast cancer stage at diagnosis. Alcohol Clin Exp Res 22: 928-934, 1998

    Google Scholar 

  15. Kuper H, Ye W, Weiderpass E, Ekbom A, Trichopoulos D, Nyren O, Adami HO: Alcohol and breast cancer risk: the alcoholism paradox. Br J Cancer 83: 949-951, 2000

    Google Scholar 

  16. Keydar I, Chen L, Karby S, Weiss FR, Delarea J, Radu M, Brenner HJ: Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer 15: 650-670, 1979

    Google Scholar 

  17. Luo J, Miller MW: Ethanol enhances erbB-mediated migration of human breast cancer cells in culture. Breast Cancer Res Treat 63: 61-69, 2000

    Google Scholar 

  18. Adickes ED, Mollner TJ, Lockwood SK: Closed chamber system for delivery of ethanol to cell culture. Alcohol 23: 377-381, 1988

    Google Scholar 

  19. Luo J, Miller MW: Ethanol inhibits basic fibroblast growth factor-mediated proliferation of C6 astrocytoma cells. J Neurochem 67: 1448-1456, 1996

    Google Scholar 

  20. Miller MW, Nowakowski RS: Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex. Alcohol Clin Exp Res 15: 229-232, 1991

    Google Scholar 

  21. Luo J, Miller MW: Basic fibroblast growth factor-and plateletderived growth factor-mediated cell proliferation in B104 neuroblastoma cells: effects of ethanol on cell cycle kinetics. Brain Res 770: 139-150, 1997

    Google Scholar 

  22. Liu W-M, Chu W-M, Choudary PV, Schmid CW: Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Res 23: 1758-1765, 1995

    Google Scholar 

  23. Liang P, Averboukh L, Keyomarsi K, Sager R, Pardee AB: Differential display and cloning of messenger RNAs from hu man breast cancer versus mammary epithelial cells. Cancer Res 52: 6966-6968, 1992

    Google Scholar 

  24. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 215: 403-410, 1990

    Google Scholar 

  25. Dani C, Blanchard JM, Piechaczyk M, EL Sabouty S, Marty L, Jeanteur PH: Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 81: 7046-7050, 1984

    Google Scholar 

  26. Ausubel FM, Brent R, Kingston RE, Moore DD, Smith JA, Seidman JS, Struhl K (eds): Current Protocols in Molecular Biology. Wiley, New York, 1994

    Google Scholar 

  27. Hahn GM, Shiu EC, Auger EA: Mammalian stress proteins HSP70 and HSP28 co-induced by nicotine and either ethanol or heat. Mol Cell Biol 11: 6034-6040, 1991

    Google Scholar 

  28. Su CY, Chong KY, Owen OE, Dillmann WH, Chang C, Lai CC: Constitutive and inducible hsp70s are involved in oxidative resistance evoked by heat shock and ethanol. J Mol Cell Cardiol 30: 587-598, 1998

    Google Scholar 

  29. Li T-H, Spearow J, Rub in CM, Schmid CW: Physiological stresses increase mouse short interspersed element (SINE) RNA expression in vivo. Gene 239: 367-372, 1999

    Google Scholar 

  30. Wool IG: Extraribosomal functions of ribosomal proteins. Trends Biochem Sci 21: 164-165, 1996

    Google Scholar 

  31. Frodin M, Gammeltoft S: Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol 151: 65-77, 1999

    Google Scholar 

  32. Noara H, Naora H: Involvement of ribosomal proteins in regulating cell growth and apoptosis: translational modulation or recruitment for extraribosomal activity? Immunol Cell Biol 77: 197-205, 1999

    Google Scholar 

  33. Chiao PJ, Sh in DM, Sacks PG, Hong WK, Tainsky MA: Elevated expression of the ribosomal protein S2 gene in human tumors. Mol Carcinogenesis 5: 219-231, 1992

    Google Scholar 

  34. Barnard GF, Staniunas RJ, Mori M, Puder M, Jessup MJ, Steele GD Jr, Chen LB: Gastric and hepatocellular carcinomas do not over-express the same ribosomal protein messenger RNAs as colonic carcinoma. Cancer Res 53: 4048-4052, 1993

    Google Scholar 

  35. Wong JM, Mafune K, Yow H, Rivers EN, Ravikumar TS, Steele GD Jr, Chen LB: Ubiquitin-ribosomal-protein S27a gene over expressed in human colorectal carcinoma is an early growth-responsive gene. Cancer Res 53: 1916-1920, 1993

    Google Scholar 

  36. Wang Y, Cheong D, Chan S, Hooi SC: Ribosomal protein L7a gene is up-regulated but not fused to the tyrosine kinase receptor as chimeric trk oncogen in human colorectal carcinoma. Int J Oncol 16: 757-762, 2000

    Google Scholar 

  37. Kondoh N, Schweinfest CW, Henderson KW, Papas TS: Differential expression of S19 ribosomal protein, laminin-binding protein, and human lymphocyte antigen class I messenger RNAs associated with colon carcinoma progression and differentiation. Cancer Res 52: 791-796, 1992

    Google Scholar 

  38. Clausse N, Jackers P, Jares P, Joris B, Sobel ME, Castronovo V: Identification of the active gene coding for the metastasisassociated 37LRP/p40 multifunctional protein. DNA Cell Biol 15: 1009-1023, 1996

    Google Scholar 

  39. Barnard GF, Staniunas RJ, Bao S, Mafune K, Steele GD Jr, Gollan JL, Chen LB: Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma. Cancer Res 52: 3067-3072, 1992

    Google Scholar 

  40. Chester KA, Robson L, Begent RHJ, Talbot IC, Pringle JH, Primrose L, Macpherson AJ, Boxer G, Southall P, Malcolm AD: Identification of a human ribosomal protein mRNA with increased expression in colorectal tumors. Biochim Biophys Acta 1009: 297-300, 1989

    Google Scholar 

  41. Pogue-geile K, Geiser JR, Shu M, Miller C, Wool IG, Meisler AI, Pipas JM: Ribosomal genes are over-expressed in colorectal cancer: isolation of a cDNA encoding human S3 ribosomal protein. Mol Cell Biol 11: 3842-3849, 1991

    Google Scholar 

  42. Kroes RA, Jastrow A, Mclone MG, Yamamoto H, Colley P, Kersey DS, Yong VW, Mkrdichian E, Cerullo L, Leestma J, Moskal JR: The identification of novel therapeutic targets for the treatment of malignant brain tumors. Cancer Lett 156: 191-198, 2000

    Google Scholar 

  43. Henry JL, Coggin DL, King CR: High expression of the ribosomal protein L19 in human breast tumors that over-express erbB-2. Cancer Res 53: 1403-1408, 1993

    Google Scholar 

  44. Vaarala MH, Porvari KS, Kyllönen AP, Mustonen MVJ, Lukkarinen O, Vihko P: Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples. Int J Cancer 78: 27-32, 1998

    Google Scholar 

  45. Ben-Ishai R, Scharf R, Sharon R, Kapten L: A human cellular sequence implicated in trk oncogene activation is DNA damage inducible. Proc Natl Acad Sci USA 87: 6039-6043, 1990

    Google Scholar 

  46. Strickland PT: Photocarcinogenesis by near-ultraviolet (UVA) radiation in Sencar mice. J Invest Dermatol 87: 272-275, 1986

    Google Scholar 

  47. Noonan FP, Otsuka T, Bang S, Anver MR, Merlino G: Accelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth factor/scatter factor transgenic mice. Cancer Res 60: 3738-3743, 2000

    Google Scholar 

  48. Moustacchi E: DNA damage and repair: consequences on dose-responses. Mutat Res 464: 35-40, 2000

    Google Scholar 

  49. Gupta RC, Lutz WK: Background DNA damage for endogenous and unavoidable exogenous carcinogens: a basis for spontaneous cancer incidence? Mutat Res 4: 1-8, 1999

    Google Scholar 

  50. Kozma SC, Redmond SMS, Xiao-Chang F, Saurer SM, Groner B, Hynes NE: Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences. EMBO J 7: 147-154, 1988

    Google Scholar 

  51. Chazenbalk GD, Wadsworth HL, Rapoport B: Tyrotropininduced expression of a gene for a ribosomal protein related to the trk oncogen. Mol Cell Endocrinol 68: 25-30, 1990

    Google Scholar 

  52. Burris T, Nawaz Z, Tsal M-J, O'Malley BW: A nuclear hormone receptor-associate protein that inhibits transactivation by the thyroid hormone and retinoic acid receptors. Proc Natl Acad Sci USA 92: 9525-9529, 1995

    Google Scholar 

  53. Zhang XK, Liu Y, Lee MO: Retinoid receptors in human lung and breast cancer. Mutat Res 350: 267-277, 1996

    Google Scholar 

  54. Martinez MB, Ruan M, Fitzpatrick LA: Altered response to thyroid hormones by prostate and breast cancer cells. Cancer Chemother Pharmacol 45: 93-102, 2000

    Google Scholar 

  55. Brook PJ: DNA damage, DNA repair, and alcohol toxicity-a review. Alcohol Clin Exp Res 21: 1073-1082, 1997

    Google Scholar 

  56. Wright RM, McManaman JL, Repine JE: Alcohol-induced breast cancer: a proposed mechanism. Free Radic Biol Med 26: 348-354, 1999

    Google Scholar 

  57. Navasumrit P, Ward TH, Dodd NJ, O'Connor PJ: Ethanolinduced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure. Carcinogenesis 21: 93-99, 2000

    Google Scholar 

  58. Purohit V: Moderate alcohol consumption and estrogen levels in postmenopausal women: a review. Alcohol Clin Exp Res 22: 994-997, 1998

    Google Scholar 

  59. Fan S, Meng Q, Gao B, Grossman J, Yadegarri M, Goldberg ID, Rosen EM: Alcohol stimulates estrogen receptor signaling in human breast cancer cells lines. Cancer Res 60: 5635-5639, 2000

    Google Scholar 

  60. Singletary K, Frey R, Yan W: Effect of ethanol on proliferation and estrogen receptor-alpha expression in human breast cancer cells. Cancer Lett 165: 131-137, 2001

    Google Scholar 

  61. Petit FG, Metivier R, Valotaire Y, Pakdel F: Synergism between a half-site and imperfect estrogen-responsive element, and cooperation with COUP-TFI are required for estrogen receptor I (ER) to activate a maximal estrogen-stimulation of rainbow trout ER gene. Eur J Biochem 259: 385-395, 1999

    Google Scholar 

  62. Singletary K: Ethanol and experimental breast cancer: a review. Alcohol Clin Exp Res 21: 334-339, 1997

    Google Scholar 

  63. Seitz HL, Pöschl G, Simanowski UA: Alcohol and cancer. In: Galanter (ed) The Consequence of Alcoholism. Plenum Press, New York, Vol 14, 1998, pp 3-95

    Google Scholar 

  64. Yirmya R, Ben-Eliyahu S, Gale R, Shavit Y, Liebeskind J, Taylor A: Ethanol increases tumor progression in rats: possible involvement of natural killer cells. Brain Behav Immun 6: 74-86, 1992

    Google Scholar 

  65. Meng Q, Gao B, Goldberg ID, Rosen EM, Fan S: Stimulation of cell invasion and migration by alcohol in breast cancer cells. Biochem Biophys Res Commun 273: 448-453, 2000

    Google Scholar 

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  1. Department of Anatomy, West Virginia University School of Medicine, Morgantown, WV, USA

    Yunfeng Zhu, Hong Lin, Zheng Li, Mei Wang & Jia Luo

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Zhu, Y., Lin, H., Li, Z. et al. Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells. Breast Cancer Res Treat 69, 29–38 (2001). https://doi.org/10.1023/A:1012293507534

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