MMP-14 and TGFβ-1 methylation in pituitary adenomas

Abstract

Abstract. Pituitary adenoma (PA) is one of the most common abnormalities in the sellar region. Despite the fact that PA is a benign monoclonal neoplasm, it can cause serious complications, including ophthalmological, neurological and endocrinological abnormalities. Currently, the causes that increase the progression of tumors are unknown. Epigenetic silencing of the matrix metalloproteinase-14 (MMP-14) and transforming growth factor beta-1 (TGFβ-1) genes may be associated with the development of PA, since these genes are important in the processes of tumor metastasis and angiogenesis. The purpose of the present study was to determine if the methylation status of the MMP-14 and TGFβ-1 promoters is associated with PA development. In the present study, 120 tissue samples of PA were used. The methylation status of the MMP-14 and TGFβ-1 promoters was investigated by methylation specific-polymerase chain reaction. Statistical analysis was conducted to investigate the associations between the methylation status, age and gender of PA patients, PA tumoral activity, recurrence and invasiveness. The MMP-14 gene was methylated in 30.00% (17/56 functioning and 19/64 non-functioning) of patients with PA, while the TGFβ-1 gene was methylated in 13.33% (9/56 functioning and 7/64 non-functioning) of patients with PA. It was also observed that promoter methylation of MMP-14 correlated with the male gender (58.8 vs. 35.7%, P=0.022), while unmethylated (non-silenced) MMP-14 correlated with the female gender (64.3 vs. 41.7%, P=0.027). Associations between the promoter methylation status of the MMP-14 and TGFβ-1 genes and PA functioning or recurrence were not identified. The present study reveals that silencing of the MMP-14 gene correlates with patients' gender. However, MMP-14 and TGFβ-1 promoter methylation cannot be considered as a prognostic marker in PAs.

Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

“…It has been demonstrated that NNMT-mediated methylation is an important conjugation reaction in the biotransformation of a number of drugs and xenobiotics, including pyridine and other structurally-associated compounds (18). The epigenetic silencing of TGF-β1 genes is associated with the development of pituitary adenoma (33). In the present study, it was hypothesized that NNMT-mediated changes in DNA methylation may be involved in TGF-β-induced EMT in gastric cancer cells.…”

The Epigenomics of Pituitary Adenoma

“…Methylation and expression levels of the N-myc Downstream-Regulated Gene 2 (NDRG2) and Signal Transducer and Activator of Transcription 3 (STAT3) promoters are also uncorrelated, along with a lack of correlation with clinical factors (86, 87). Methylation of the Matrix Metallopeptidase 14 (MMP-14) and Transforming Growth Factor Beta 1 (TGF β -1) promoters was also not associated with tumor functionality or recurrence (88). Hypermethylation of the Human Telomerase Reverse Transcriptase (hTERT ) promoter, which can contribute to cellular immortalization and tumorigenesis, has also been noted across different pituitary tumor subtypes but has not been associated with significant differences in tumor parameters, tumor subtype, or prognosis (89).…”

Tumor Angiogenesis in Pituitary Adenoma

“…It is affect DDR1 ligand combined with DDR1 can promote the DDR1 signaling pathway. DDR1 promotes MMP-2/9 expression, leading to ECM reconstruction and tumor invasion [25][26][27]. Cell apoptosis, change tumor cell invasiveness, and regulation of energy metabolism is mediated by hypoxic condition.…”