Expression dynamics of Mage family genes during self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells

Abstract

The biological roles of cancer-testis antigens of the Melanoma antigen (Mage) family in mammalian development, stem cell differentiation and carcinogenesis are largely unknown. In order to understand the involvement of the Mage family genes in maintenance of normal and cancer stem cells, the expression patterns of Mage-a, Mage-b, Mage-d, Mage-e, Mage-h and Mage-l gene subfamilies were analyzed during the self-renewal and differentiation of mouse pluripotent stem and teratocarcinoma cells. Clustering analysis based on the gene expression profiles of undifferentiated and differentiating cell populations revealed strong correlations between Mage expression patterns and differentiation and malignant states. Gene co-expression analysis disclosed the potential contributions of Mage family members in self-renewal and differentiation of pluripotent stem and teratocarcinoma cells. Two gene clusters including Mage-a4 and Mage-a8, Mageb1, Mage-d1, Mage-d2, Mage-e1, Mage-l2 were identified as functional antagonists with opposing roles in the regulation of proliferation and differentiation of mouse pluripotent stem and teratocarcinoma cells. The identified aberrant expression patterns of Mage-a2, Mage-a6, Mage-b4, Mageb-16 and Mage-h1 in teratocarcinoma cells can be considered as specific teratocarcinoma biomarkers promoted the malignant phenotype. Our study first provides a model for the involvement of Mage family members in regulatory networks during the self-renewal and early differentiation of normal and cancerous stem cells for further research of the predicted functional modules and the development of new cancer treatment strategies.

<p>MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma</p>

“…Over the past decades, the MAGE protein family, which is a highly conserved group of proteins that share a common MAGE homology domain, has led to numerous insights that MAGEs were involved not only in stem cell differentiation and tumorigenesis progression, but also in invasion and metastasis. 26,27 MAGE-A11, the unique steroid hormone receptor transcriptional coregulator among the type I MAGEs, is known to be involved in the transcriptional activity of androgen receptor (AR) by binding with p160 in prostate cancer. [28][29][30] Furthermore, MAGE-A11, as a transcriptional activator of E2F1 and androgen receptor, interacts with retinoblastoma-related protein p107 and enhances prostate cancer cell growth.…”

The impact of oxytocin on neurite outgrowth and synaptic proteins in Magel2‐deficient mice

“…Therefore, insufficient ATRA action on neurite outgrowth in Magel2-deficient mice could be associated with potential downstream alterations in vesicle trafficking, as well as the corresponding increased lipid droplet accumulation and changes in neuronal morphology observed in the study by Crutcher et al (2019). Interestingly enough, it has been reported that ATRA can stimulate the expression of Mage family genes, including the Magel2 in various cell lines in vitro (Gordeeva et al, 2019), suggesting that Magel2 is downstream of the ATRA pathway. In this study, we observed decreased expression of Limk1 and Tiam1, which are enzymes known to be associated with rearranging of the cytoskeleton (see scheme in Figure 11) and interact with the retinoid receptor function (Ishaq et al, 2011).…”

“…(2019). Interestingly enough, it has been reported that ATRA can stimulate the expression of Mage family genes, including the Magel2 in various cell lines in vitro (Gordeeva et al., 2019), suggesting that Magel2 is downstream of the ATRA pathway. In this study, we observed decreased expression of Limk1 and Tiam1 , which are enzymes known to be associated with rearranging of the cytoskeleton (see scheme in Figure 11) and interact with the retinoid receptor function (Ishaq et al., 2011).…”

The Impact of Oxytocin on Neurite Outgrowth and Synaptic Proteins inMagel2-Deficient Mice

“…(2019). Interestingly enough, it has been reported that ATRA can stimulate the expression of Mage family genes, including the Magel2 in various cell lines in vitro (Gordeeva, Gordeev & Khaydukov, 2019), suggesting that Magel2 is downstream of the ATRA pathway. In this study, we observed decreased expression of Limk1 and Tiam1, which are enzymes known to be associated with rearranging of the cytoskeleton (see scheme in figure 11) and interact with the retinoid receptor function (Ishaq et al, 2011).…”