Molecular Biotechnology

, Volume 56, Issue 1, pp 64–71 | Cite as

Analysis of HOX Gene Expression Patterns in Human Breast Cancer

  • Ho Hur
  • Ji-Yeon Lee
  • Hyo Jung Yun
  • Byeong Woo Park
  • Myoung Hee KimEmail author


HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior–posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression.


HOX Breast cancer Expression analysis Cell lines Normal breast tissue Malignant breast tissue 



This research was supported by funds from the National Health Insurance Service Ilsan Hospital (2010-01), the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Education, Science and Technology (2010-0026759, 2010-0025149, 2013008399), and partly by a Grant from the BioGreen 21 Program, RDA, Korea (PJ00905601).


  1. 1.
    Rao, R. D., & Cobleigh, M. A. (2012). Adjuvant endocrine therapy for breast cancer. Oncology, 26, 541–547.Google Scholar
  2. 2.
    Slamon, D., Eiermann, W., Robert, N., Pienkowski, T., Martin, M., Press, M., et al. (2011). Adjuvant trastuzumab in HER2-positive breast cancer. New England Journal of Medicine, 365, 1273–1283.CrossRefGoogle Scholar
  3. 3.
    Giuliano, M., Schifp, R., Osborne, C. K., & Trivedi, M. V. (2011). Biological mechanisms and clinical implications of endocrine resistance in breast cancer. Breast, S3, S42–S49.CrossRefGoogle Scholar
  4. 4.
    Rexer, B. N., & Arteaga, C. L. (2012). Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: Mechanisms and clinical implications. Critical Reviews in Oncogenesis, 17, 1–16.CrossRefGoogle Scholar
  5. 5.
    Mann, R. S., & Affolter, M. (1998). Hox proteins meet more partners. Current Opinion in Genetics & Development, 8, 423–429.CrossRefGoogle Scholar
  6. 6.
    Favier, B., & Dollé, P. (1997). Developmental functions of mammalian Hox genes. Molecular Human Reproduction, 3, 115–131.CrossRefGoogle Scholar
  7. 7.
    Shah, N., & Sukumar, S. (2010). The Hox genes and their roles in oncogenesis. Nature Reviews Cancer, 10, 361–371.CrossRefGoogle Scholar
  8. 8.
    Svingen, T., & Tonissen, K. F. (2003). Altered HOX gene expression in human skin and breast cancer cells. Cancer Biology & Therapy, 2, 518–523.CrossRefGoogle Scholar
  9. 9.
    Cantile, M., Procino, A., Feliciello, I., Cindolo, L., & Cillo, C. (2003). In vivo expression of the whole HOX gene network in human breast cancer. European Journal of Cancer, 39, 257–264.CrossRefGoogle Scholar
  10. 10.
    Makiyama, K., Hamada, J., Takada, M., Murakawa, K., Takahashi, Y., Tada, M., et al. (2005). Aberrant expression of HOX genes in human invasive breast carcinoma. Oncology Reports, 13, 673–679.Google Scholar
  11. 11.
    Raman, V., Martensen, S. A., Reisman, D., Evron, E., Odenwald, W. F., Jaffee, E., et al. (2000). Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature, 405, 974–978.CrossRefGoogle Scholar
  12. 12.
    Gilbert, P. M., Mouw, J. K., Unger, M. A., Lakins, J. N., Gbegnon, M. K., Clemmer, V. B., et al. (2010). HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype. Journal of Clinical Investigation, 120, 1535–1550.CrossRefGoogle Scholar
  13. 13.
    Care, A., Silvani, A., Meccia, E., Mattia, G., Peschle, C., & Colombo, M. P. (1998). Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence. Oncogene, 16, 3285–3289.CrossRefGoogle Scholar
  14. 14.
    Jin, K., Kong, X., Shah, T., Penet, M. F., Wildes, F., Sgroi, D. C., et al. (2012). The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proceedings of the National Academy of Sciences of the United States of America, 109, 2736–2741.CrossRefGoogle Scholar
  15. 15.
    Carè, A., Felicetti, F., Meccia, E., Bottero, L., Parenza, M., Stoppacciaro, A., et al. (2001). HOXB7: A key factor for tumor-associated angiogenic switch. Cancer Research, 61, 6532–6539.Google Scholar
  16. 16.
    Hayashida, T., Takahashi, F., Chiba, N., Brachtel, E., Takahashi, M., Godin-Heymann, N., et al. (2010). HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proceedings of the National Academy of Sciences of the United States of America, 107, 1100–1105.CrossRefGoogle Scholar
  17. 17.
    Zhang, X., Zhu, T., Chen, Y., Mertani, H. C., Lee, K. O., & Lobie, P. E. (2003). Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. Journal of Biological Chemistry, 278, 7580–7590.CrossRefGoogle Scholar
  18. 18.
    Shaoqiang, C., Yue, Z., Yang, L., Hong, Z., Lina, Z., Da, P., et al. (2013). Expression of HOXD3 correlates with shorter survival in patients with invasive breast cancer. Clinical & Experimental Metastasis, 30, 155–163.CrossRefGoogle Scholar
  19. 19.
    Rodriguez, B. A., Cheng, A. S., Yan, P. S., Potter, D., Agosto-Perez, F. J., Shapiro, C. L., et al. (2008). Epigenetic repression of the estrogen-regulated Homeobox B13 gene in breast cancer. Carcinogenesis, 29, 1459–1465.CrossRefGoogle Scholar
  20. 20.
    Kao, J., Salari, K., Bocanegra, M., Choi, Y. L., Girard, L., Gandhi, J., et al. (2009). Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One, 4, e6146.CrossRefGoogle Scholar
  21. 21.
    Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., et al. (2006). A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell, 10, 515–527.CrossRefGoogle Scholar
  22. 22.
    Hsiao, Y. H., Chou, M. C., Fowler, C., Mason, J. T., & Man, Y. G. (2010). Breast cancer heterogeneity: Mechanisms, proofs, and implications. Journal of Cancer, 1, 6–13.CrossRefGoogle Scholar
  23. 23.
    Morgan, R., Boxall, A., Harrington, K. J., Simpson, G. R., Gillett, C., Michael, A., et al. (2012). Targeting the HOX/PBX dimer in breast cancer. Breast Cancer Research and Treatment, 136, 389–398.CrossRefGoogle Scholar
  24. 24.
    Di Pietro, M., Lao-Sirieix, P., Boyle, S., Cassidy, A., Castillo, D., Saadi, A., et al. (2012). Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus. Proceedings of the National Academy of Sciences of the United States of America, 109, 9077–9082.CrossRefGoogle Scholar
  25. 25.
    Boimel, P. J., Cruz, C., & Segall, J. E. (2011). A functional in vivo screen for regulators of tumor progression identifies HOXB2 as a regulator of tumor growth in breast cancer. Genomics, 98, 164–172.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ho Hur
    • 1
    • 3
  • Ji-Yeon Lee
    • 2
  • Hyo Jung Yun
    • 2
  • Byeong Woo Park
    • 3
  • Myoung Hee Kim
    • 2
    Email author
  1. 1.Department of SurgeryNational Health Insurance Service Ilsan HospitalGoyangKorea
  2. 2.Embryology Laboratory, Department of Anatomy, and Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulKorea
  3. 3.Department of SurgeryYonsei University College of MedicineSeoulKorea

Personalised recommendations