Regulation of matrix metealloproteinase 14 gene by TGF-β cytokine

Matrix Metalloproteinase (MMP) enzyme group, which is one of the proteolytic systems involved in the hydrolysis of ECM components, consists of 24 members. MMPs are calcium (Ca+2) and zinc (Zn+2) dependent neutral endopeptidase groups and although they are divided into different groups, they have common features when examined structurally. MMP14, also known as MT1-MMP, which is a member of the membrane type MMP family, is localized in the 14q11,2 region of the 14th chromosome, consists of 11009 base pairs and has 10 exons. MMP14 is expressed as a 60 kDa zymogen. MMP14, which has a low expression level in normal cells, has a high expression level in cancer cells. Since MMP14 is the only membrane-bound collagenase; it increases tumor invasiveness and regulates the growth of metastatic tumors. Decreased oxygen level, also known as hypoxia, is also seen in physiological and pathophysiological processes. When tumor cells are not exposed to sufficient oxygen levels, they create genetic differences before cell death and thus adapt to the hypoxic condition. Because of this adaptation, some tumors have been shown to develop resistance to chemotherapeutic or radiotherapy treatments. Transforming growth factor β (TGF-β) is a bifunctional cytokine that both inhibits and promotes cell proliferation. TGF-β, which acts as a tumor suppressor in normal epithelial cells; it regulates adhesion, proliferation, differentiation, senescence and apoptosis. The change in the expression of MMP14 under hypoxic and normoxic conditions in PC-3 cells, a postal cancer cell line, was investigated within the scope of our study. For this purpose, MMP14 promoter fragments of different lengths were created and cloned promoter fragments were transfected into cells for functional activity studies. Basal transcriptional activities were determined. By applying 500U TGF-β cytokine to PC-3 cells under normal and hypoxic conditions, changes in MMP14 and HIF-1α mRNA levels in cells were determined by Real Time PCR; The changes in protein level were determined by IFC. In addition, the effect of TGF-β on MMP14 promoter fragments was also investigated.