THE INTERFERENCE OF B-ARRESTIN2 EXPRESSION AND THE RESPONSE TO TMZ TREATMENT IN HIGH GRADE GLIOMA
DOI:
https://doi.org/10.52701/monc.2021.v2i2.42Keywords:
glioblastoma, ?-arrestin, transfection, overexpression, temozolomideAbstract
Beta-arrestins (B-arr) are a group of proteins which play an important role in the GPCR regulation. They have been shown to facilitate cancer progression in many organs. Although the correlation between malignant gliomas and the effect of B-arr is not solidified, several studies presented an interesting effect when temozolomide treatment is intersected with B-arr 2 overexpression in cancer cells. In our study, we transfected the U-343MGa cell line with B-arr 2, in order to observe its effect in concordance with temolozomide treatment. The cells were observed at three different time points, 24h, 48h and 72h, regarding their cell viability. Initially, at the 24h time point, the B-arr 2 overexpression produced a mild cytotoxic effect, but at the 48h time point a sudden increase in cell proliferation was recorded. The 72h time point left us with another slight drop in cell proliferation. The interaction with different doses of TMZ produced a variety of results, no apparent correlation being observed. In conclusion, the effect of B-arr 2 transfection in malignant gliomas is an important matter to be further studied, in order to better understand the underlying processes of cancer progression.
References
Alexandru O, Purcaru SO, Tataranu LG, Lucan L, Castro J, Folcuti C, et al. The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma. Int J Mol Sci. 2018;19(1).
https://doi.org/10.3390/ijms19010229
Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in cancer treatment. Clinical therapeutics. 2016;38(7):1551-66.
https://doi.org/10.1016/j.clinthera.2016.03.026
Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by ß-arrestins. Science. 2005;308(5721):512-7.
https://doi.org/10.1126/science.1109237
Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, et al. Activation and targeting of extracellular signal-regulated kinases by ?-arrestin scaffolds. Proceedings of the National Academy of Sciences. 2001;98(5):2449-54.
https://doi.org/10.1073/pnas.041604898
Nusse R, Clevers H. Wnt/?-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;169(6):985-99.
https://doi.org/10.1016/j.cell.2017.05.016
Bryja V, Gradl D, Schambony A, Arenas E, Schulte G. ?-Arrestin is a necessary component of Wnt/?-catenin signaling in vitro and in vivo. Proceedings of the National Academy of Sciences. 2007;104(16):6690-5.
https://doi.org/10.1073/pnas.0611356104
Rosanò L, Cianfrocca R, Tocci P, Spinella F, Di Castro V, Caprara V, et al. Endothelin A receptor/?-arrestin signaling to the Wnt pathway renders ovarian cancer cells resistant to chemotherapy. Cancer research. 2014;74(24):7453-64.
https://doi.org/10.1158/0008-5472.CAN-13-3133
Zou L, Yang R, Chai J, Pei G. Rapid xenograft tumor progression in beta?arrestin1 transgenic mice due to enhanced tumor angiogenesis. The FASEB Journal. 2008;22(2):355-64.
https://doi.org/10.1096/fj.07-9046com
Nawaz Z, Patil V, Paul Y, Hegde AS, Arivazhagan A, Santosh V, et al. PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326 as a tumour suppressor miRNA. Molecular cancer. 2016;15(1):1-16.
https://doi.org/10.1186/s12943-016-0557-8
Cianfrocca R, Tocci P, Semprucci E, Spinella F, Di Castro V, Bagnato A, et al. ?-Arrestin 1 is required for endothelin-1-induced NF-?B activation in ovarian cancer cells. Life sciences. 2014;118(2):179-84.
https://doi.org/10.1016/j.lfs.2014.01.078
Zhang Y-X, Li X-F, Yuan G-Q, Hu H, Song X-Y, Li J-Y, et al. ?-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition. Journal of Biological Chemistry. 2017;292(21):8933-47.
https://doi.org/10.1074/jbc.M116.770420
Lan T, Wang H, Zhang Z, Zhang M, Qu Y, Zhao Z, et al. Downregulation of ?-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling. Experimental cell research. 2017;357(1):51-8.
https://doi.org/10.1016/j.yexcr.2017.04.023
Cong L, Qiu Z-y, Zhao Y, Wang W-b, Wang C-x, Shen H-c, et al. Loss of ?-arrestin-2 and activation of CXCR2 correlate with lymph node metastasis in non-small cell lung cancer. Journal of Cancer. 2017;8(14):2785.
https://doi.org/10.7150/jca.19631
Czogalla B, Partenheimer A, Jeschke U, von Schönfeldt V, Mayr D, Mahner S, et al. ?-arrestin 2 is a prognostic factor for survival of ovarian cancer patients upregulating cell proliferation. Frontiers in endocrinology. 2020;11:658.
https://doi.org/10.3389/fendo.2020.554733
Hong F, Zhang Y, Cheng W, Sun X, Wang J. ?-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice. BMC cancer. 2019;19(1):1-9.
https://doi.org/10.1186/s12885-019-6254-4
„Horescu C, Elena Cioc C, Tuta C, Sevastre AS, Tache DE, Alexandru O, et al. The effect of temozolomide in combination with doxorubicin in glioblastoma cells in vitro. J Immunoassay Immunochem.2020;41(6):1033-43.
https://doi.org/10.1080/15321819.2020.1819309
„Alexandru O, Sevastre AS, Castro J, Artene SA, Tache DE, Purcaru OS, et al. Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines. Int J Mol Sci. 2019;20(19).
https://doi.org/10.3390/ijms20194663
Artene SA, Turcu-Stiolica A, Ciurea ME, Folcuti C, Tataranu LG, Alexandru O, et al. Comparative effect of immunotherapy and standard therapy in patients with high grade glioma: a meta-analysis of published clinical trials. Sci Rep. 2018;8(1):11800.
https://doi.org/10.1038/s41598-018-30296-x
de Castro Sant'Anna C, Junior AGF, Soares P, Tuji F, Paschoal E, Chaves LC, et al. Molecular biology as a tool for the treatment of cancer. Clinical and experimental medicine. 2018;18(4):457-64.
https://doi.org/10.1007/s10238-018-0518-1
Nalejska E, M?czy?ska E, Lewandowska MA. Prognostic and predictive biomarkers: tools in personalized oncology. Molecular diagnosis & therapy.2014;18(3):273-84.
https://doi.org/10.1007/s40291-013-0077-9
Luttrell LM, Lefkowitz RJ. The role of ?-arrestins in the termination and transduction of G-protein-coupled receptor signals. Journal of cell science. 2002;115(3):455-65. https://doi.org/10.1242/jcs.115.3.455
Peterson YK, Luttrell LM. The diverse roles of arrestin scaffolds in G protein-coupled receptor signaling. Pharmacological reviews. 2017;69(3):256-97.https://doi.org/10.1124/pr.116.013367
Fereshteh M, Ito T, Kovacs JJ, Zhao C, Kwon HY, Tornini V, et al. ?-Arrestin2 mediates the initiation and progression of myeloid leukemia. Proceedings of the National Academy of Sciences. 2012;109(31):12532-7.
https://doi.org/10.1073/pnas.1209815109
„Lakshmikanthan V, Zou L, Kim JI, Michal A, Nie Z, Messias NC, et al. Identification of ?Arrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proceedings of the National Academy of Sciences. 2009;106(23):9379-84.
https://doi.org/10.1073/pnas.0900258106
„Grossmann ME, Huang H, Tindall DJ. Androgen receptor signaling in androgen-refractory prostate cancer. Journal of the National Cancer Institute. 2001;93(22):1687-97.
https://doi.org/10.1093/jnci/93.22.1687
„Purayil HT, Zhang Y, Black JB, Gharaibeh R, Daaka Y. Nuclear ?Arrestin1 regulates androgen receptor function in castration resistant prostate cancer. Oncogene. 2021;40(14):2610-20.
https://doi.org/10.1038/s41388-021-01730-8
„Bonnans C, Flacelière M, Grillet F, Dantec C, Desvignes J-P, Pannequin J, et al. Essential requirement for ?-arrestin2 in mouse intestinal tumors with elevated Wnt signaling. Proceedings of the National Academy of Sciences. 2012;109(8):3047-52.
https://doi.org/10.1073/pnas.1109457109
Bae W-Y, Choi J-S, Nam S, Jeong J-W. ?-arrestin 2 stimulates degradation of HIF-1? and modulates tumor progression of glioblastoma. Cell Death & Differentiation. 2021:1-13.
https://doi.org/10.1038/s41418-021-00802-2
Artene S, Folcuti C, DRICU A. ?-arrestin 1 Overexpression Increases Temozolomide Resistance in Human Malignant Glioma Cells. Current health sciences journal. 2017;43(2):112.
Horescu C, Artene S-A. The effect of beta-arrestin 1 transfection on proliferation and temozolomide treatment response in HGG cells. Medico Oncology. 2020;1(1):1-9. https://doi.org/10.52701/monc.2020.v1i1.5
Folcuti C, Horescu C, Barcan E, Alexandru O, Tuta C, Vatu B-I, et al. ?-arrestin 1 transfection induced cell death in high grade glioma in vitro. Journal of Immunoassay and Immunochemistry. 2020;41(6):1021-32.
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