Abstract
Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (−1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (−1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.
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Abbreviations
- MMP-9:
-
Matrix metalloproteinase-9
- SNP:
-
Single nucleotide polymorphism
- AS-PCR:
-
Allele-specific polymerase chain reaction
References
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60:277–300.
Gaurav A, Pooja R, Ernesto R, Sa'nchez F, Jorge Carrasco R'n, Juan Manuel C, et al. Breast cancer care in developing countries. World J Surg. 2009;33:2069–76.
Agarwal G, Ramakant P. Breast cancer care in India: the current scenario and the challenges for the future. Breast Care. 2008;3:21–7.
Byrne C, Brinton LA, Haile RW, Schairer C. Heterogeneity of the effect of family history on breast cancer risk. Epidemiology. 1991;2:276–84.
Smith P, McGuffog L, Douglas F, Easton, et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer. 2006;45:646–55.
Pakseresht S, Ingle GK, Bahadur AK, Ramteke VK, Singh MM, Garg S, et al. Risk factors with breast cancer among women in Delhi. Indian J Cancer. 2009;46:132–8.
Althuis DM, Dozier JM, Anderson FW, Devesa SS, Brinton LA. Global trends in breast cancer incidence and mortality. Int J Epidemiol. 1973–1997; 34:405–12.
Maller O, Martinson H, Schedin P. Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland. J Mammary Gland Biol Neoplasia. 2010;15:301–18.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Forget MA, Desrosiers RR, Beliveau R. Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis. Can J Physiol Pharmacol. 1999;77:465–80.
Kohn EC, Liotta LA. Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res. 1995;55:1856–62.
Chaudhary AK et al. Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview. Mutat Res Rev. 2013;753(1):7–23. doi:10.1016/j.mrrev.2013.01.002.
Jed F. Fisher, Shahriar Mobashery. Recent advances in MMP inhibitor design, Cancer Metastasis Rev.2006; 115–36.
Ajay Kumar Chaudhary, Mamta Singh, Alok C Bharti, Kamlesh Asotra, Shanthy Sundaram and Ravi Mehrotra. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck, J Biol Chem. 2010; 17–10.
Nagase H, Woessner Jr JF. Matrix metalloproteinase. J Biol Chem. 1999;274:21491–4.
Jones JL, Walker RA. Control of matrix metalloproteinase activity in cancer. J Pathol. 1997;183:377–9.
McDonnell S, Navre M, Coffey Jr RJ, Matrisian LM. Expression and localization of matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. Mol Carcinog. 1991;4:527–33.
Tu HF, Wu CH, Kao SY, Liu CJ, Liu TY, Lui MT. Functional −1562 C-to-T polymorphism in matrix metalloproteinase-9 (MMP-9) promoter is associated with the risk for oral squamous cell carcinoma in younger male areca users. J Oral Pathol Med. 2007;36:409–14.
Wu J, Zhang L, Luo H, Zhu Z, Zangh C, Hou Y. Association of matrix metalloproteinases-9 gene polymorphisms with genetic susceptibility to esophageal squamous cell carcinoma. DNA Cell Biol. 2008;27:553–7.
Liu Z, Li L, Yang Z, et al. Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. 2010;10:270.
Kallakury BV et al. Increased expression of Matrix metalloproteinase 2 & 9 and tissue inhibitors of matrix metalloproteinase 1 & 2 correlates with poor prognostic variables in renal cell carcinoma. Clin Cancer Res. 2001;7:3113–9.
Baker EA, Leaper DJ. Measuring gelatinase activity in colorectal cancer. Eur J Surg Oncol. 2002;28:24–9.
Tanioka Y, Yoshida T, Yagawa T, Saiki Y, Takeo S, Harada T, et al. Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer. Br J Cancer. 2003;89:2116–21.
Ozalp S, Tanir HM, Yalcin OT, Kabukcuoglu S, Oner U, Uray M. Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors. Eur J Gynaecol Oncol. 2003;24:417–20.
Sakata K, Satoh M, Someya M, Asanuma H, Nagakura H, Oouchi A, et al. Expression of matrix metalloproteinase 9 is a prognostic factor in patients with non-Hodgkin lymphoma. Cancer. 2004;100:356–65.
Lahiri DK, Nurnberger Jr JI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19:5444.
Raković MŽA, Stanković A. Allele-specific detection of C-1562T polymorphism in the matrix metalloproteinase-9 gene: genotyping by MADGE. Clin Biochem. 2006;39:630–2.
McCawley LJ, Matrisian LM. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today. 2000;6:149–56.
Venkateshwari AK, Sri M, Krishnaveni D, Pratibha N, Vidyasagar A, Jyothy A. Role of plasma MMP 9 levels in the pathogenesis of chronic pancreatitis. Ind J Clin Biochem. 2011;26:136–9.
Turpeenniemi-Hujanen T. Gelatinases (MMP-2 and −9) and their natural inhibitors as prognostic indicators in solid cancers. Biochimie. 2005;87:287–97.
Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathological features and survival. Clin Med Res. 2009;7:4–13.
Henderson IC, Patek AJ. The relationship between prognostic and predictive factors in the management of breast cancer. Breast Cancer Res Treat. 1998;52:261–88.
Rose DP, Royak-Schaler R. Tumor biology and prognosis in black breast cancer patients: a review. Cancer Detect Prev. 2001;25:16–31.
Zhang S, Li L, Lin JY, Lin H. Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma. World J Gastroenterol. 2003;9:899–04.
Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, et al. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation. 1999;99:1788–94.
Baker EA, Leaper DJ. The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer. 2003;39:981–8.
Zhou Y, Chunyuan Y, Miao X, Tan W, Liang G, Xiong P, et al. Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes. Carcinogenesis. 2004;25:399–04.
Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol. 2000;10:415–33.
Srivastava P, Mandhani A, Kapoor R, Mittal RD. Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort. Ann Surg Oncol. 2010;17:3068–75.
Przybylowska K, Kluczna A, Zadrozny M, Krawczyk T, Kulig A, Rykala J, et al. Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Res Treat. 2006;95:65–72.
Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res. 2006;26:3579–83.
Ishimaru H, Kageyama Y, Hayashi T, Nemoto T, Eishi Y, Kihara K. Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases. Acta Oncol. 2002;41:289–96.
Gum R, Lengyel E, Juarez J, Chen JH, Sato H, Seiki M, et al. Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences. J Biol Chem. 1996;271:10672–80.
Shibao TK, Tsurudome Y, Hirata K, Nagata N, Itoh H. Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis Colon Rectum. 2007;50:308–14.
Shu Y. Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res. 2006;69:636–45.
Acknowledgments
This work was supported by grants from the University Grants Commission (UGC), Rajeev Gandhi National Fellowship (RGNF), New Delhi, India; Department of Bio-Technology (DBT), Osmania University-Inter Disciplinary School for Life Science for Advance Research and Education (ISLARE), New Delhi; and UGC Center for Advanced Studies (CAS) II, New Delhi.
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Chiranjeevi, P., Spurthi, K.M., Rani, N.S. et al. Gelatinase B (−1562C/T) polymorphism in tumor progression and invasion of breast cancer. Tumor Biol. 35, 1351–1356 (2014). https://doi.org/10.1007/s13277-013-1181-5
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DOI: https://doi.org/10.1007/s13277-013-1181-5