Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Expression of Fragile Histidine Triad (FHIT) and WW-Domain Oxidoreductase Gene (WWOX) in Nasopharyngeal Carcinoma

  • Chen, Xu (Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University) ;
  • Li, Ping (Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University) ;
  • Yang, Zheng (Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University) ;
  • Mo, Wu-Ning (Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University)
  • Published : 2013.01.31
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Abstract

The aim of the present study was to analyze the expression of FHIT and WWOX in nasopharyngeal carcinoma (NPC) and correlations with clinical pathologic features. mRNA expression of the FHIT and WWOX was assessed by real-time fluorescent relatively quantitative PCR in 61 NPC tissues and 45 non-cancerous nasopharyngeal tissues. As a result, mRNA expression levels of both FHIT and WWOX were significantly lower in NPC patients than in control samples (P=0.049 and 0.045, respectively). Moreover, the mRNA expression of both had an inverse relation with larger invasive range (P=0.035 and 0.048, respectively), poor histologic differentiation (P=0.012 and 0.016) and advanced clinical stage (P=0.026 and 0.038). Consistency was found between expression of FHIT and WWOX in the same NPC tissues (r=0.681, P=0.00). In conclusion, synergy between FHIT and WWOX may exist in the development of NPC so that the two factors may be considered as important genetic markers. Detecting the expression of FHIT and WWOX should provide clinically significant information relevatn to tumor diagnosis, progression and treatment modalities for NPC.

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References

  1. Aqeilan RI, Croce CM (2007). WWOX in biological control and tumorigenesis. J Cell Physiol, 212, 307-10. https://doi.org/10.1002/jcp.21099
  2. Aqeilan RI, Donati V, Palamarchuk A, et al (2005). WWdomain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res, 65, 6764-72. https://doi.org/10.1158/0008-5472.CAN-05-1150
  3. Aqeilan RI, Hagan JP, Aqeilan HA, et al (2007). Inactivation of the Wwox gene accelerates forestomach tumor progression in vivo. Cancer Res, 67, 5606-10. https://doi.org/10.1158/0008-5472.CAN-07-1081
  4. Aqeilan RI, Hassan MQ, de Bruin A, et al (2008). The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J Biol Chem, 283, 21629-39. https://doi.org/10.1074/jbc.M800855200
  5. Aqeilan RI, Pekarsky Y, Herrero JJ, et al (2004). Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci USA, 101, 4401-6. https://doi.org/10.1073/pnas.0400805101
  6. Aqeilan RI, Palamarchuk A, Weigel RJ, et al (2004). Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. Cancer Res, 64, 8256-61. https://doi.org/10.1158/0008-5472.CAN-04-2055
  7. Aqeilan RI, Trapasso F, Hussain S, et al (2007). Targeted deletion of Wwox reveals a tumor suppressor function. Proc Natl Acad Sci USA, 104, 3949-54. https://doi.org/10.1073/pnas.0609783104
  8. Baffa R, Veronese ML, Santoro R, et al (1998). Loss of FHIT expression in gastric carcinoma. Cancer Res, 58, 4708-14.
  9. Barnes LD, Garrison PN, Siprashvili Z, et al (1996). Fhit, a putative tumor suppressor in humans, is a dinucleoside 50,50 00-P1, P3-triphosphate hydrolase. Biochemistry, 35, 11529-35. https://doi.org/10.1021/bi961415t
  10. Bednarek AK, Keck-Waggoner CL, Daniel RL, et al (2001). WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res, 61, 8068-73.
  11. Bednarek AK, Laflin KJ, Daniel RL, et al (2000). WWOX, a novel WW domain-containing protein mapping to human chromosome 16q2.33-2.41, a region frequently affected in breast cancer. Cancer Res, 60, 2140-5.
  12. Bloomston M, Kneile J, Butterfield M, et al (2009).Coordinate loss of fragile gene expression in pancreatobiliary cancers:correlations among markers and clinical features. Ann Surg Oncol, 16, 2331-8. https://doi.org/10.1245/s10434-009-0507-4
  13. Campiglio M, Pekarsky Y, Menard S, et al (1999). FHIT loss of function in human primary breast cancer correlates with advanced stage of the disease. Cancer Res, 59, 3866-9.
  14. Cantor JP, Iliopoulos D, Rao AS, et al (2007). Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity. Int J Cancer, 120, 24-31. https://doi.org/10.1002/ijc.22073
  15. Cho WC (2007). Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer, 6, 1.
  16. Connolly DC, Greenspan DL, Wu R, et al (2000). Loss of Fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease. Clin Cancer Res, 6, 3505-10.
  17. Donati V, Fontanini G, Dell'Omodarme M, et al (2007). WWOX expression in different histologic types and subtypes of nonsmall cell lung cancer. Clin Cancer Res, 13, 884-91. https://doi.org/10.1158/1078-0432.CCR-06-2016
  18. Driouch K, Prydz H, Monese R, et al (2002). Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors. Oncogene, 21, 1832-40. https://doi.org/10.1038/sj.onc.1205273
  19. Dumon KR, Ishii H, Fong LY, et al (2001). FHIT gene therapy prevents tumor development in Fhit-deficient mice. Proc Natl Acad Sci USA, 98, 3346-51. https://doi.org/10.1073/pnas.061020098
  20. Guler G, Uner A, Guler N, et al (2004). The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma. Cancer, 100, 1605-14. https://doi.org/10.1002/cncr.20137
  21. Huebner K, Croce C (2001). FRA3B and other common fragile sites: the weakest links. Nat Rev Cancer, 1, 214 -21.
  22. Guler G, Uner A, Guler N, et al (2005). Concordant loss of fragile gene expression early in breast cancer development. Pathol Int, 55, 471-8. https://doi.org/10.1111/j.1440-1827.2005.01855.x
  23. Huebner K, Druck T, Siprashvili Z, et al (1998). The role of deletions at the FRA3B/FHIT locus in carcinogenesis. Recent Results Cancer Res, 154, 200-15. https://doi.org/10.1007/978-3-642-46870-4_12
  24. Huebner K, Garrison PN, Barnes LD, Croce CM (1998). The role of the FHIT/FRA3B locus in cancer. Annu Rev Genet, 32, 7-31. https://doi.org/10.1146/annurev.genet.32.1.7
  25. Huebner K, Hadaczek P, Siprashvili Z, Druck T, Croce CM (1997). The FHIT gene, a multiple tumor suppressor gene encompassing the carcinogen sensitive chromosome fragile site, FRA3B. Biochim Biophys Acta, 1332, M65-70.
  26. Iliopoulos D, Guler G, Han SY, et al (2005). Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Oncogene, 24, 1625-33. https://doi.org/10.1038/sj.onc.1208398
  27. Ilsley JL, Sudol M, Winder SJ (2002). The WW domain: linking cell signaling to the membrane cytoskeleton. Cell Signaling, 513, 30-7.
  28. Ishii H, Vecchione A, Furukawa Y, et al (2003). Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Mol Cancer Res, 1, 940-7.
  29. Kurek KC, Del Mare S, Salah Z, et al (2010). Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Res, 70, 5577-86. https://doi.org/10.1158/0008-5472.CAN-09-4602
  30. Kuroki T, Trapasso F, Shiraishi T, et al (2002). Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. Cancer Res, 62, 2258-60.
  31. Kuroki T, Yendamuri S, Trapasso F, et al (2004). The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin Cancer Res, 10, 2459-65. https://doi.org/10.1158/1078-0432.CCR-03-0096
  32. Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM (2003). WWOX, the common chromosomal fragile site, FRA16D, cancer gene. Cytogenet Genome Res, 100, 101-10. https://doi.org/10.1159/000072844
  33. Ludes-Meyers JH, Kil H, Bednarek AK, et al (2004). WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. Oncogene, 23, 5049-55. https://doi.org/10.1038/sj.onc.1207680
  34. Macias MJ, Wiesner S, Sudol M (2002). WW and domains, two different scaffolds to recogniaz praline-rich ligands. FEBS Lett, 513, 30-7. https://doi.org/10.1016/S0014-5793(01)03290-2
  35. Man S, Ellis IO, Sibbering M, Blamey RW, Brook JD (1996). High levels of allele loss at the FHIT and ATM genes in non-comedo ductal carcinoma in situ and grade I tubular invasive breast cancers. Cancer Res, 56, 5484-9.
  36. Mark B, Jeffrey K, Matthew B, et al (2009). Coordinate Loss of Fragile Gene Expression in Pancreatobiliary Cancers: Correlations Among Markers and Clinical Features. Ann Surg Oncol, 16, 2331-8 https://doi.org/10.1245/s10434-009-0507-4
  37. Michael D, Beer DG, Wilke CW, Miller DE, Glover TW (1997). Frequent deletions of FHIT and FRA3B in Barrett's metaplasia and esophageal adenocarcinomas. Oncogene, 15, 1653-9. https://doi.org/10.1038/sj.onc.1201330
  38. Mori M, Mimori K, Shiraishi T, et al (2000). Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus. Cancer Res, 60, 1177-82.
  39. Nakayama S, Semba S, Maeda N, et al (2008). Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells. Cancer Sci, 99, 1370-6. https://doi.org/10.1111/j.1349-7006.2008.00841.x
  40. Noguchi T, Muller W, Wirtz HC, Willers R, Gabbert HE (1999). FHIT gene in gastric cancer: association with tumour progression and prognosis. J Pathol, 188, 378-81. https://doi.org/10.1002/(SICI)1096-9896(199908)188:4<378::AID-PATH378>3.0.CO;2-B
  41. Nunez MI, Ludol-Meyer J, Abba MC, et al (2005). Frequent loss of WWOX expression in breast cancer correlation with estrogen receptor status. Breast Cancer Res Treat, 89, 99-150. https://doi.org/10.1007/s10549-004-1474-x
  42. Nunez MI, Ludes-Meyers J, Aldaz CM (2006). WWOX protein expression in normal human tissues. J Mol Histol, 37, 115-25. https://doi.org/10.1007/s10735-006-9046-5
  43. Nunez MI, Rosen DG, Ludes-Meyers JH, et al (2005).WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer, 5, 64. https://doi.org/10.1186/1471-2407-5-64
  44. Ohta M, Inoue H, Cotticelli MG, et al (1996). The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t (3; 8) breakpoint, is abnormal in digestive tract cancers. Cell, 84, 587-97. https://doi.org/10.1016/S0092-8674(00)81034-X
  45. Ozaki K, Enomoto T, Yoshino K, et al (2001). Impaired FHIT expression characterizes serous ovarian carcinoma. Br J Cancer, 85, 247-54. https://doi.org/10.1054/bjoc.2001.1886
  46. Paige AJ, Taylor KJ, Taylor C, et al (2001). WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci USA, 98, 11417-22. https://doi.org/10.1073/pnas.191175898
  47. Pluciennik E, Kusinska R, Potemski P, et al (2006).WWOX-the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis. Eur J Surg Oncol, 32, 153-7. https://doi.org/10.1016/j.ejso.2005.11.002
  48. Popescu NC (2003). Genetic alterations in cancer as a result of breakage at fragile sites. Cancer Lett, 192, 1-17. https://doi.org/10.1016/S0304-3835(02)00596-7
  49. Pylkkanen L, Wolff H, Stjernvall T, et al (2002) Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients. Int J Oncol, 20, 285-90.
  50. Qin HR, Iliopoulos D, Nakamura T, et al (2007). WWOX suppresses prostate cancer cell growth through modulation of ErbB2-mediated androgen receptor signaling. Mol Cancer Res, 5, 957-65. https://doi.org/10.1158/1541-7786.MCR-07-0211
  51. Ramos D, Aldaz CM (2006). WWOX, a chromosomal fragile site gene and its role in cancer. Adv Exp Med Biol, 587, 149-59 https://doi.org/10.1007/978-1-4020-5133-3_14
  52. Solomon E, Borrow J, Goddard AD (1991). Chromosome aberrations and cancer. Science, 25, 1153-60.
  53. Sozzi G, Pastorino U, Moiraghi L, et al (1998). Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res, 58, 5032-37.
  54. Sozzi G, Tornielli S, Tagliabue E, et al (1997). Absence of Fhit protein in primary lung tumor and cell lines with FHIT gene abnormalities. Cancer Res, 57, 5207-12.
  55. Tseng JE, Kemp BL, Khuri FR, et al (1999). Loss of Fhit is frequent in stage I non-small cell lung cancer and in the lungs of chronic smokers. Cancer Res, 59, 4798-803.
  56. Tuner BC, Ottey M, Zmonjic DB, et al (2002). The fragile histidine triad/common chromo some fragile site 3B locus and repair-deficient cancer. Cancer Res, 62, 4054-60.
  57. Wang TT, Frezza EE, Ma R, et al (2008) Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities. Chin Med J, 121, 1969-74.
  58. Yendamuri S, Kuroki T, Trapasso F, et al (2003). WW domain containing oxidoreductase gene expression is altered in nonsmall cell lung cancer. Cancer Res, 63, 878-81.
  59. Yunis JJ, Soreng AL (1984). Constitutive fragile sites and cancer. Science, 226, 1199-204. https://doi.org/10.1126/science.6239375

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