Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Increased Expression of HOXB2 and HOXB13 Proteins is Associated with HPV Infection and Cervical Cancer Progression

  • Gonzalez-Herrera, A.L. (Laboratorio de Oncologia Molecular, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS) ;
  • Salgado-Bernabe, M. (Laboratorio de Oncologia Molecular, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS) ;
  • Velazquez-Velazquez, C.K. (Laboratorio de Oncologia Molecular, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS) ;
  • Salcedo-Vargas, M. (Laboratorio de Oncologia Genomica, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS) ;
  • Andrade-Manzano, A. (Departamento de Patologia Hospital de Ginecoobstetricia no. IMSS) ;
  • Avila-Moreno, F. (Laboratorio de Epigenomica del Cancer, Unidad de Biomedicina FES-Iztacala, UNAM) ;
  • Pina-Sanchez, P. (Laboratorio de Oncologia Molecular, Unidad de Investigacion Medica en Enfermedades Oncologicas CMN S XXI IMSS)
  • Published : 2015.03.09
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Abstract

Background: Cervical cancer (CeCa) is the second most common cancer in women in developing countries, and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. Materials and Methods: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. Results: Percentage of HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. Conclusions: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.

Keywords

References

  1. Alami Y, Castronovo V, Belotti D, et al (1999). HOXC5 and HOXC8 expression are selectively turned on in human cervical cancer cells compared to normal keratinocytes. Biochem Biophys Res Commun, 257, 738-45. https://doi.org/10.1006/bbrc.1999.0516
  2. Ali F, Kuelker R and Wassie B (2012). Understanding cervical cancer in the context of developing countries. Ann Trop Med PH, 5, 3. https://doi.org/10.4103/1755-6783.92871
  3. Barba-de la Rosa AP, Briones-Cerecero E, Lugo-Melchor O, et al. (2012). Hox B4 as potential marker of non-differentiated cells in human cervical cancer cells. J Cancer Res Clin Oncol, 138, 293-300. https://doi.org/10.1007/s00432-011-1081-2
  4. Cantile M, Franco R, Tschan A, et al (2009). HOX D13 expression across 79 tumor tissue types. Int J Cancer, 125, 1532-41. https://doi.org/10.1002/ijc.24438
  5. Chung SH, Wiedmeyer K, Shai A, et al (2008). Requirement for estrogen receptor ${\alpha}$ in a mouse model for human papillomavirus-associated cervical cancer. Cancer Res, 68, 9928-34. https://doi.org/10.1158/0008-5472.CAN-08-2051
  6. Daftary GS and Taylor HS (2006). Endocrine regulation of HOX genes. Endocr Rev, 27, 331-55. https://doi.org/10.1210/er.2005-0018
  7. Davenne M, Maconochie MK, Neun R, et al (1999). Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain. Neuron, 4, 22.
  8. Economides KD, and Capecchi MR (2003). Hoxb13 is required for normal differentiation and secretory function of the ventral prostate. Development, 130, 2061-9. https://doi.org/10.1242/dev.00432
  9. Favier B and Dolle P (1997). Developmental functions of mammalian Hox genes. Mol Hum Reprod, 3, 115-131. https://doi.org/10.1093/molehr/3.2.115
  10. Ferlay J, Soerjomataram I, Ervik M, et al (2014). GLOBOCAN 2012 v1. 0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International agency for research on cancer. c2013 [cited 2013 Oct 17]. globocan. iarc. fr.
  11. Gehring WJ (1987). Homeoboxes in the study of development. Science, 236, 1245-52 https://doi.org/10.1126/science.2884726
  12. Gehring WJ, Muller M, Affolter M et al (1990). The structure of the homeodomain and its functional implications. Trends Genet, 6, 323-9. https://doi.org/10.1016/0168-9525(90)90253-3
  13. Hidalgo A, Baudis M, Petersen I, et al (2005). Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma. BMC Cancer, 5, 77. https://doi.org/10.1186/1471-2407-5-77
  14. Hyland PL, McDade S, McCloskey R, et al (2011). Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes. J Virology, 85, 10999-11006. https://doi.org/10.1128/JVI.00160-11
  15. Inamura K, Togashi Y, Ninomiya H, et al (2008). HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells. Anticancer Res, 28, 2121-7.
  16. Inamura K, Togashi Y, Okui M, et al (2007). HOXB2 as a novel prognostic indicator for stage I lung adenocarcinomas. J Thorac Oncol, 2, 802-7. https://doi.org/10.1097/JTO.0b013e3181461987
  17. Kim SD, Park RY, Kim Y, et al (2010). HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression. Anat Cell Biol, 43, 284-93. https://doi.org/10.5115/acb.2010.43.4.284
  18. Kim YR, Kim IJ, Kang TW, et al (2013). HOXB13 downregulates intracellular zinc and increases NF-${\kappa}B$ signaling to promote prostate cancer metastasis. Oncogene, 33, 4458-67.
  19. Krumlauf R (1994). Hox genes in vertebrate development. Cell, 29, 191-201.
  20. Kuglik P, Smetana J, Vallova V, et al (2014). Genome-wide screening of DNA copy number alterations in cervical carcinoma patients with CGH+ SNP microarrays and HPV-SH. Int J Clin Exp Pathol, 7, 5071.
  21. Lopez R, Garrido E, Pina P et al (2006). HOXB homeobox gene expression in cervical carcinoma. Int J Gynecol Cancer, 16, 329-35. https://doi.org/10.1111/j.1525-1438.2006.00350.x
  22. Luhn P, Walker J, Schiffman M, et al (2013). The role of cofactors in the progression from human papillomavirus infection to cervical cancer. Gynecol Oncol, 128, 265-270. https://doi.org/10.1016/j.ygyno.2012.11.003
  23. Ma L, Benson GV, Lim H et al (1998). Abdominal B (AbdB) hoxagenes: regulation in adult uterus by estrogen and progesterone and repression in mullerian duct by the synthetic estrogen diethylstilbestrol (DES). Dev Biol, 197, 141-54. https://doi.org/10.1006/dbio.1998.8907
  24. Ma XJ, Hilsenbeck SG, Wang W et al (2006). The HOXB13: IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol, 24, 4611-9. https://doi.org/10.1200/JCO.2006.06.6944
  25. Mack JA, Li L, Sato N et al (2005). Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation in an epidermal organotypic model. J Biol Chem, 280, 29904-11. https://doi.org/10.1074/jbc.M505262200
  26. Mann R S, Lelli KM, Joshi R (2009). Hox specificity: unique roles for cofactors and collaborators. Curr Top Dev Biol, 88, 63-101. https://doi.org/10.1016/S0070-2153(09)88003-4
  27. Miao J, Wang Z, Provencher H, et al (2007). HOXB13 promotes ovarian cancer progression. Proc Nat Acad Sci USA, 104, 17093-8. https://doi.org/10.1073/pnas.0707938104
  28. Perez-Plasencia C, Vazquez-Ortiz G, Lopez-Romero R, et al (2007). Genome wide expression analysis in HPV16 cervical cancer: identification of altered metabolic pathways. Infect Agent Cancer, 2, 16. https://doi.org/10.1186/1750-9378-2-16
  29. Pina Sanchez P, Hernandez-Hernandez DM, Lopez-Romero R, et al (2006). Human papillomavirus-specific viral types are common in Mexican women affected by cervical lesions. Int J Gynecol Cancer, 16, 1041-7. https://doi.org/10.1111/j.1525-1438.2006.00458.x
  30. Policht FA, Song M, Sitailo S. et al (2010). Analysis of genetic copy number changes in cervical disease progression. BMC cancer, 10, 432. https://doi.org/10.1186/1471-2407-10-432
  31. Segara D, Biankin AV, Kench JG, et al (2005). Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia. Clin Cancer Res, 11, 3587-96. https://doi.org/10.1158/1078-0432.CCR-04-1813
  32. Shah N, Sukumar S. (2010). The Hox genes and their roles in oncogenesis. Nature Reviews Cancer, 10, 361-71. https://doi.org/10.1038/nrc2826
  33. Shah N, Jin K, Cruz LA, et al (2013). HOXB13 mediates tamoxifen resistance and invasiveness in human breast cancer by suppressing ER${\alpha}$ and inducing IL-6 expression. Cancer Res, 73, 5449-58. https://doi.org/10.1158/0008-5472.CAN-13-1178
  34. Shim C, Zhang W, Rhee CH, et al (1998). Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res, 4, 3045-50.
  35. Walboomers JM, Jacobs MV, Manos M. et al (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189, 12-9. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
  36. Weiwei Y, Jinhui L, Xiaoliang X, et al (2009). Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Practice, 205, 709-15. https://doi.org/10.1016/j.prp.2009.05.010
  37. Zhai Y, Kuick, R, Nan B, et al (2007). Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Res, 67, 10163-72. https://doi.org/10.1158/0008-5472.CAN-07-2056
  38. Zhao L, Zhu S, Gao Y, et al (2014). Two-gene expression ratio as predictor for breast cancer treated with tamoxifen: evidence from meta-analysis. Tumor Biol, 35, 3113-7. https://doi.org/10.1007/s13277-013-1403-x
  39. zur Hausen H (2009b). Papillomaviruses in the causation of human cancers - a brief historical account. Virology, 384, 260-5. https://doi.org/10.1016/j.virol.2008.11.046

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