Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.
Department of Human Pathology of Adult and Childhood "Gaetano Barresi," University of Messina, 98125 Messina, Italy.
Int J Mol Sci. 2020 Feb 18;21(4):1364. doi: 10.3390/ijms21041364.
Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, , cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non--amplified) and IMR-32 (-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.
转谷氨酰胺酶 2（TG2）是一种多功能酶，在癌症组织中已经揭示了两种同工型，即 TG2-L 和 TG2-S，它们在细胞死亡和存活的调节中发挥相反的作用。值得注意的是，在癌细胞中，缺氧环境可能会刺激肿瘤的生长、侵袭和转移。在这里，我们旨在研究 TG2 同工型在缺氧条件下对神经母细胞瘤细胞命运的作用。在缺氧/复氧条件下，检测了 SH-SY5Y（非扩增）和 IMR-32（扩增）神经母细胞瘤细胞中 TG2 同工型、缺氧诱导因子（HIF）-1α、细胞周期蛋白 D1 和 B1 的 mRNA 水平，以及细胞增殖/死亡、DNA 损伤和细胞周期的标志物。在两种细胞系中，缺氧都诱导了的上调。缺氧条件导致 SH-SY5Y 细胞中 TG2-S 的上调和细胞活力/增殖的减少，与 DNA 损伤相关，而在 IMR-32 中不产生 DNA 损伤，并增加了两种 TG2 同工型和增殖标志物的水平。不同的细胞对缺氧的反应可以通过 TG2 同工型在的扩增状态下的功能来介导。对 TG2 同工型在神经母细胞瘤中的作用的更好理解可能会在诊断和治疗方面开辟新的途径。
