Breast Cancer Research and Treatment

, Volume 95, Issue 1, pp 65–72 | Cite as

Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer

  • Karolina Przybylowska
  • Anita Kluczna
  • Marek Zadrozny
  • Tadeusz Krawczyk
  • Andrzej Kulig
  • Jan Rykala
  • Agnieszka Kolacinska
  • Zbigniew Morawiec
  • Jozef Drzewoski
  • Janusz Blasiak
Article

Summary

Purpose

Matrix metalloproteinases play a crucial role in the cancer invasion and metastasis, angiogenesis and tumorigenicity. A single guanine insertion – the 1G/2G polymorphism in the promoter of the matrix metalloproteinase 1 (MMP-1) gene creates a binding site for the transcription factor AP-1 and thus may affect the transcription level of MMP-1. The C→T substitution at the polymorphic site of the MMP-9 gene promoter results in a higher transcription activity of the T-allelic promoter trough the loss of binding site for a repressor protein. The aim of this work was to investigate the influence of 1G/2G and C→T polymorphisms on the MMP-1 and MMP-9 level and therefore on the occurrence and progression of breast cancer.

Experimental design

We investigated the distribution of genotypes and frequency of alleles of the 1G/2G and C→T polymorphisms for 270 patients with breast cancer and 300 healthy women served as control. The genotypes were determined by RFLP-PCR. Additionally, we estimated the level of MMP-1 and MMP-9 antigens in tumor samples and normal breast tissue using ELISA.

Results

The levels of MMP-1 in tumor samples of node positive patients ware significantly higher than in samples of node negative patients (p<0.05). Increased level of MMP-9 correlates with Bloom-Richardson grading III (p<0.05), increased tumor size (p<0.05) and absence of estrogen and progesterone receptors (p<0.01). Additionally, both MMP-1 and MMP-9 levels were higher in tumor than in the normal breast tissue. We showed the higher risk of metastasis development in lymph node for the 2G/2G genotype (OR=2.14; CI 95% 1.24;3.69) and the 2G allele carriers (OR=1.68; CI 95% 1.19;2.39). We found correlation between the T allele (OR=2.61; CI 95% 1.33;4.87), 2G (OR=2.58; CI 95% 1.35;4.91) and malignance.

Conclusion

The results suggest that MMP-1 is responsible for the local invasion and MMP-9 is associated with the malignance and the growth of the tumor. We suggest that the 2G allele of the 1G/2G MMP-1 gene polymorphism may be associated with the lymph node metastasis in patients with breast cancer and therefore it can be considered as a progression marker in this disease.

Key words:

breast cancer gene polymorphism matrix metalloproteinases (MMPs) MMP-1 gene MMP-9 gene tumour progression 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Karolina Przybylowska
    • 1
  • Anita Kluczna
    • 1
  • Marek Zadrozny
    • 2
  • Tadeusz Krawczyk
    • 2
  • Andrzej Kulig
    • 2
  • Jan Rykala
    • 3
  • Agnieszka Kolacinska
    • 3
  • Zbigniew Morawiec
    • 3
  • Jozef Drzewoski
    • 4
  • Janusz Blasiak
    • 1
  1. 1.Department of Molecular GeneticsUniversity of LodzLodzPoland
  2. 2.Polish Mother’s Memorial Hospital – Research InstituteLodzPoland
  3. 3.Department of Surgical OncologyN. Copernicus Memorial HospitalLodzPoland
  4. 4.Department of Clinical PharmacologyMedical University of LodzLodzPoland

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