Matrix Metallopeptidase 3 Polymorphisms: Emerging genetic Markers in Human Breast Cancer Metastasis

Abstract

Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.

Keywords: Breast; Carcinoma; Matrix metalloproteinase 3; Neoplasm metastasis.

Figure 1. The domain structure of MMP3 (adapted from Visse and Nagase, 2003). The domain organization of MMP3 includes S, Pro, Cat, Hpx.

MMP3 = matrix metallopeptidase 3; S = translocation signal peptide; Pro = propeptide; Cat = catalytic domain; Hpx = hemopexin domain.

Figure 2. Schematic representatives of MMP3 gene with localisation of single nucleotide polymorphisms [43].

MMP3 = matrix metallopeptidase 3; mRNA = messenger RNA.