MMP-14 and TGFβ-1 methylation in pituitary adenomas

Ruskyte,Kornelija; Liutkevicienė,Rasa; Vilkeviciute,Alvita; Vaitkiene,Paulina; Valiulytė,Indre; Glebauskiene,Brigita; Kriauciuniene,Loresa; Zaliuniene,Dalia

doi:10.3892/ol.2016.4919

MMP-14 and TGFβ-1 methylation in pituitary adenomas

Authors:
- Kornelija Ruskyte
- Rasa Liutkevicienė
- Alvita Vilkeviciute
- Paulina Vaitkiene
- Indre Valiulytė
- Brigita Glebauskiene
- Loresa Kriauciuniene
- Dalia Zaliuniene
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Affiliations: Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, Lithuania, Department of Ophthalmology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, Lithuania, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, Lithuania
Published online on: July 29, 2016 https://doi.org/10.3892/ol.2016.4919
Pages: 3013-3017

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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.

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1	Nistor R: Pituitary tumors. Neuro Rew. 57:264–272. 1996.
2	Kovacs K, Scheithauer BW, Horvath E and Lloyd RV: The world health organization classification of adenohypophysial neoplasms: A proposed five-tier scheme. Cancer. 78:502–510. 1996. View Article : Google Scholar : PubMed/NCBI
3	Monteiro ML, Moura FC and Cunha LP: Frequency doubling perimetry in patients with mild and moderate pituitary tumor-associated visual field defects detected by conventional perimetry. Arq Bras Oftalmol. 70:323–329. 2007. View Article : Google Scholar : PubMed/NCBI
4	Jagannathan J, Dumont AS, Prevedello DM, Lopes B, Oskouian RJ, Jane JA Jr and Laws ER Jr: Genetics of pituitary adenomas: Current theories and future implications. Neurosurg Focus. 19:E42005.PubMed/NCBI
5	Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R and Kaur G: Matrix metalloproteinases and cancer-roles in threat and therapy. Asian Pac J Cancer Prev. 15:1085–1091. 2014. View Article : Google Scholar : PubMed/NCBI
6	Nam DH and Ge X: Direct production of functional matrix metalloproteinase-14 without refolding or activation and its application for in vitro inhibition assays. Biotechnol Bioeng. 113:717–723. 2016. View Article : Google Scholar : PubMed/NCBI
7	Lehti K, Allen E, Birkedal-Hansen H, Holmbeck K, Miyake Y, Chun TH and Weiss SJ: An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. Genes Dev. 19:979–991. 2005. View Article : Google Scholar : PubMed/NCBI
8	Sabeh F, Ota I, Holmbeck K, Birkedal-Hansen H, Soloway P, Balbin M, Lopez-Otin C, Shapiro S, Inada M, Krane S, et al: Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. J Cell Biol. 167:769–781. 2004. View Article : Google Scholar : PubMed/NCBI
9	Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mason MD and Mansel RE: Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells. Int J Mol Med. 17:583–590. 2006.PubMed/NCBI
10	Massagué J: TGFbeta in Cancer. Cell. 134:215–230. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wakefield LM and Roberts AB: TGF-beta signaling: Positive and negative effects on tumorigenesis. Curr Opin Genet Dev. 12:22–29. 2002. View Article : Google Scholar : PubMed/NCBI
12	Johnson MD, Shaw AK, O'Connell MJ, Sim FJ and Moses HL: Analysis of transforming growth factor beta receptor expression and signaling in higher grade meningiomas. J Neurooncol. 103:277–285. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J and Seoane J: High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 11:147–160. 2007. View Article : Google Scholar : PubMed/NCBI
14	Wu Y, Li Q, Zhou X, Yu J, Mu Y, Munker S, Xu C, Shen Z, Müllenbach R, Liu Y, et al: Decreased levels of active SMAD2 correlate with poor prognosis in gastric cancer. PLoS One. 7:e356842012. View Article : Google Scholar : PubMed/NCBI
15	Recouvreux MV, Lapyckyj L, Camilletti MA, Guida MC, Ornstein A, Rifkin DB, Becu-Villalobos D and Díaz-Torga G: Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas. Endocrinology. 154:4192–4205. 2013. View Article : Google Scholar : PubMed/NCBI
16	Wilson CB: Neurosurgical management of large and invasive pituitary tumors. Clinical Management of Pituitary Disorders. Tindall GT and Collins WF: New York Raven Press. (New York). 335–342. 1979.
17	Knosp E, Steiner E, Kitz K and Matula C: Pituitary adenomas with invasion of the cavernous sinus space: A magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 33:610–617; discussion 617–618. 1993. View Article : Google Scholar : PubMed/NCBI
18	Li LC and Dahiya R: MethPrimer: Designing primers for methylation PCRs. Bioinformatics. 18:1427–1431. 2002. View Article : Google Scholar : PubMed/NCBI
19	Page RB: Sellar and parasellar tumors. Neurosurgery. Wilkins RH and Rengachary SS: McGraw-Hill. 791–804. 1996.
20	Heaney A: Management of aggressive pituitary adenomas and pituitary carcinomas. J Neurooncol. 117:459–468. 2014. View Article : Google Scholar : PubMed/NCBI
21	Kulis M and Esteller M: DNA methylation and cancer. Adv Genet. 70:27–56. 2010. View Article : Google Scholar : PubMed/NCBI
22	Chernov AV, Sounni NE, Remacle AG and Strongin AY: Epigenetic control of the invasion-promoting MT1-MMP/MMP-2/TIMP-2 axis in cancer cells. J Biol Chem. 284:12727–12734. 2009. View Article : Google Scholar : PubMed/NCBI
23	Altaş M, Bayrak OF, Ayan E, Bolukbasi F, Silav G, Coskun KK, Culha M, Sahin F, Sevli S and Elmaci I: The effect of polymorphisms in the promoter region of the MMP-1 gene on the occurrence and invasiveness of hypophyseal adenoma. Acta Neurochir (Wien). 152:1611–1617; discussion 1617. 2010. View Article : Google Scholar : PubMed/NCBI
24	Hui P, Xu X, Xu L, Hui G, Wu S and Lan Q: Expression of MMP14 in invasive pituitary adenomas: Relationship to invasion and angiogenesis. Int J Clin Exp Pathol. 8:3556–3567. 2015.PubMed/NCBI
25	Recouvreux MV, Camilletti MA, Rifkin DB, Becu-Villalobos D and Díaz-Torga G: Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-β1 (TGF-β1). Endocrinology. 153:3861–3871. 2012. View Article : Google Scholar : PubMed/NCBI
26	Zhenye L, Chuzhong L, Youtu W, Xiaolei L, Lei C, Lichuan H, Hongyun W, Yonggang W, Fei W and Yazhuo Z: The expression of TGF-β1, Smad3, phospho-Smad3 and Smad7 is correlated with the development and invasion of nonfunctioning pituitary adenomas. J Transl Med. 12:712014. View Article : Google Scholar : PubMed/NCBI
27	Elenkova A, Atanassova I, Kirilov G, Vasilev V, Kalinov K and Zacharieva S: Transforming growth factor β1 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study). Eur J Endocrinol. 169:299–306. 2013. View Article : Google Scholar : PubMed/NCBI
28	Chen C, Zhao KN, Masci PP, Lakhani SR, Antonsson A, Simpson PT and Vitetta L: TGFβ isoforms and receptors mRNA expression in breast tumors: Prognostic value and clinical implications. BMC Cancer. 15:10102015. View Article : Google Scholar : PubMed/NCBI
29	Liu ZY, Zhang GL, Wang MM, Xiong YN and Cui HQ: MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. Asian Pac J Cancer Prev. 12:2819–2823. 2011.PubMed/NCBI
30	Wang Y, Jiang M, Li Z, Wang J, Du C, Yanyang L, Yu Y, Wang X, Zhang N, Zhao M, et al: Hypoxia and TGF-β1 lead to endostatin resistance by cooperatively increasing cancer stem cells in A549 transplantation tumors. Cell Biosci. 5:722015. View Article : Google Scholar : PubMed/NCBI
31	Xiao Y, Yuan X, Qiu H and Li Q: Single-nucleotide polymorphisms of TGFβ1 and ATM associated with radiation-induced pneumonitis: A prospective cohort study of thoracic cancer patients in China. Int J Clin Exp Med. 8:16403–16413. 2015.PubMed/NCBI
32	Sathyamoorthy T, Tezera LB, Walker NF, Brilha S, Saraiva L, Mauri FA, Wilkinson RJ, Friedland JS and Elkington PT: Membrane type 1 matrix metalloproteinase regulates monocyte migration and collagen destruction in tuberculosis. J Immunol. 195:882–891. 2015. View Article : Google Scholar : PubMed/NCBI
33	Johnson JL, Jenkins NP, Huang WC, Di Gregoli K, Sala-Newby GB, Scholtes VP, Moll FL, Pasterkamp G and Newby AC: Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability. Mediators Inflamm. 2014:2764572014. View Article : Google Scholar : PubMed/NCBI
34	Vincze C, Pál G, Wappler EA, Szabó ER, Nagy ZG, Lovas G and Dobolyi A: Distribution of mRNAs encoding transforming growth factors-beta1, −2 and −3 in the intact rat brain and after experimentally induced focal ischemia. J Comp Neurol. 518:3752–3770. 2010. View Article : Google Scholar : PubMed/NCBI