The Relationship of CAC Polymorphism in HOXA1 Gene and Breast Cancer

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

3 Assistant Professor, Department of Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

Abstract

Background: HOXA1 is a transcription factor. In the human mammary gland, the expression of the HOXA1 gene is very low or absent during normal growth and differentiation, but it is expensed at high levels in breast cancer lesions. To date, there has been no study on the relationship between CAC repeat (polyhistidine) in the first exon of HOXA1 gene and the cancer risk. The purpose of this study was to investigate polymorphism of CAC in in the first exon of HOXA1 gene among patients with breast cancer and healthy individuals to clear the relationship of CAC polymorphism in HOXA1 Gene and the risk of breast cancer.Methods: Peripheral blood samples were collected from 193 women with breast cancer and 200 healthy women. After DNA extraction from peripheral blood samples by salting-out method and amplification of desired sequence by polymerase chain reaction (PCR), the number of CAC repeat was determined by polyacrylamide gel electrophoresis and direct sequencing.Findings: Five different length of CAC repeat in the range of 3-7 and 5 allele combinations (genotypes) were observed among patients and controls. The most frequent allele in both patients and controls was the 7-CAC repeat. No significant association was observed between this allele and breast cancer risk. Statistical analyses showed significant association between homozygote 7 and estrogen and progesterone receptors.Conclusion: Our findings demonstrate that there is no significant association between CAC repeat in exon 1of HOXA1 gene and breast cancer risk. However, there is a significant association between homozygote 7 genotype and estrogen and progesterone receptors.

Keywords

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: A Cancer Journal for Clinicians 2011; 61(2): 69-90.
  2. Yavari P, Mosavizadeh M, Sadrol-Hefazi B, Mehrabi Y. Reproductive characteristics and the risk of breast cancer--a case-control study in Iran. Asian Pac J Cancer Prev 2005; 6(3): 370-5.
  3. Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: an epidemiological review. Breast J 2007; 13(4): 383-91.
  4. Campeau PM, Foulkes WD, Tischkowitz MD. Hereditary breast cancer: new genetic developments, new therapeutic avenues. Hum Genet 2008; 124(1): 31-42.
  5. Palacios J, Robles-Frias MJ, Castilla MA, Lopez-Garcia MA, Benitez J. The molecular pathology of hereditary breast cancer. Pathobiology 2008; 75(2): 85-94.
  6. Svingen T, Tonissen KF. Altered HOX gene expression in human skin and breast cancer cells. Cancer Biol Ther 2003; 2(5): 518-23.
  7. Samuel S, Naora H. Homeobox gene expression in cancer: insights from developmental regulation and deregulation. Eur J Cancer 2005; 41(16): 2428-37.
  8. Pilato B, Pinto R, De SS, Lambo R, Paradiso A, Tommasi S. HOX gene methylation status analysis in patients with hereditary breast cancer. J Hum Genet 2013; 58(1): 51-3.
  9. Lewis MT. Homeobox genes in mammary gland development and neoplasia. Breast Cancer Res 2000; 2(3): 158-69.
  10. Kelly ZL, Michael A, Butler-Manuel S, Pandha HS, Morgan RG. HOX genes in ovarian cancer. J Ovarian Res 2011; 4: 16.
  11. Bitu CC, Destro MF, Carrera M, da Silva SD, Graner E, Kowalski LP, et al. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis. BMC Cancer 2012; 12: 146.
  12. Makiyama K, Hamada J, Takada M, Murakawa K, Takahashi Y, Tada M, et al. Aberrant expression of HOX genes in human invasive breast carcinoma. Oncol Rep 2005; 13(4): 673-9.
  13. Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer 2010; 10(5): 361-71.
  14. Wardwell-Ozgo J, Dogruluk T, Gifford A, Zhang Y, Heffernan TP, van DR, et al. HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome. Oncogene 2014; 33(8): 1017-26.
  15. Marra L, Cantile M, Scognamiglio G, Perdona S, La ME, Cerrone M, et al. Deregulation of HOX B13 expression in urinary bladder cancer progression. Curr Med Chem 2013; 20(6): 833-9.
  16. Cantile M, Pettinato G, Procino A, Feliciello I, Cindolo L, Cillo C. In vivo expression of the whole HOX gene network in human breast cancer. Eur J Cancer 2003; 39(2): 257-64.
  17. Chen H, Sukumar S. Role of homeobox genes in normal mammary gland development and breast tumorigenesis. J Mammary Gland Biol Neoplasia 2003; 8(2): 159-75.
  18. Chariot A, Castronovo V. Detection of HOXA1 expression in human breast cancer. Biochem Biophys Res Commun 1996; 222(2): 292-7.
  19. Briegel KJ. Embryonic transcription factors in human breast cancer. IUBMB Life 2006; 58(3): 123-32.
  20. Delval S, Taminiau A, Lamy J, Lallemand C, Gilles C, Noë A, et al. The Pbx Interaction Motif of Hoxa1 Is Essential for Its Oncogenic Activity. PLoS ONE 2011; 6(9): 1.
  21. Srebrow A, Friedmann Y, Ravanpay A, Daniel CW, Bissell MJ. Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells. J Cell Biochem 1998; 69(4): 377-91.
  22. Perry JK, Mohankumar KM, Emerald BS, Mertani HC, Lobie PE. The contribution of growth hormone to mammary neoplasia. J Mammary Gland Biol Neoplasia 2008; 13(1): 131-45.
  23. Ren Z, Cai Q, Shu XO, Cai H, Cheng JR, Wen WQ, et al. Genetic polymorphisms in the human growth hormone-1 gene (GH1) and the risk of breast carcinoma. Cancer 2004; 101(2): 251-7.
  24. Zhu T, Starling-Emerald B, Zhang X, Lee KO, Gluckman PD, Mertani HC, et al. Oncogenic transformation of human mammary epithelial cells by autocrine human growth hormone. Cancer Res 2005; 65(1): 317-24.
  25. Pandey V, Perry JK, Mohankumar KM, Kong XJ, Liu SM, Wu ZS, et al. Autocrine human growth hormone stimulates oncogenicity of endometrial carcinoma cells. Endocrinology 2008; 149(8): 3909-19.
  26. Cheng W, Liu J, Yoshida H, Rosen D, Naora H. Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 2005; 11(5): 531-7.
  27. Zhang X, Zhu T, Chen Y, Mertani HC, Lee KO, Lobie PE. Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. J Biol Chem 2003; 278(9): 7580-90.
  28. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
  29. Paraguison RC, Higaki K, Sakamoto Y, Hashimoto O, Miyake N, Matsumoto H, et al. Polyhistidine tract expansions in HOXA1 result in intranuclear aggregation and increased cell death. Biochem Biophys Res Commun 2005; 336(4): 1033-9.
  30. Paraguison RC, Higaki K, Yamamoto K, Matsumoto H, Sasaki T, Kato N, et al. Enhanced autophagic cell death in expanded polyhistidine variants of HOXA1 reduces PBX1-coupled transcriptional activity and inhibits neuronal differentiation. J Neurosci Res 2007; 85(3): 479-87.
  31. Cho HS, Toyokawa G, Daigo Y, Hayami S, Masuda K, Ikawa N, et al. The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. Int J Cancer 2012; 131(3): E179-E189.
Journal of Isfahan Medical School
Volume 32, Issue 285 - Serial Number 285
March and April 2014
Pages 660-668

Files

History

  • Receive Date: 17 March 2014
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics