Tumor-specific MAGE proteins as regulators of p53 function

Ladelfa, María Fátima; Peche, Leticia Y.; Toledo, María Fernanda; Laiseca, Julieta Eva; Schneider, Claudio; Monte, Martín

doi:10.1016/j.canlet.2012.05.031

Cited by 35 publications

(24 citation statements)

References 69 publications

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“…However, data obtained recently suggest that specific MAGE-I members (or at least a discrete subset of them) could interfere with normal cell function by affecting distinct signaling pathways (13).…”

Section: Discussionmentioning

confidence: 99%

“…For example, MageA1 regulates Skip activity (5), MageA11 expression enhances androgen receptor transactivation function (6 -9), and MageA2 associates with and regulates p53 tumor suppressor activity (10,11) and with Pml, causing an impairment in oncogene-induced senescence (12). Overall, emerging data strongly suggest that MAGE-A proteins counteract pro-apoptotic or cell cycle-arresting stimuli (13). Accordingly, MAGE-A expression has been frequently correlated to a poor prognosis in cancer patients (14 -17).…”

Section: Mageb2 Belongs To the Melanoma Antigen Gene (Mage-i)mentioning

confidence: 99%

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Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress

Peche

Ladelfa

Toledo

et al. 2015

Journal of Biological Chemistry

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Background: MageB2 is a tumor-specific antigen with unknown function. Results: Through a mechanism involving histone deacetylases, MageB2 enhances E2F activity and resistance to Actinomycin D. Conclusion: MageB2 is a protein conferring proliferation properties and resistance to ribotoxic stress to tumor cells. Significance: Expression of MageB2 in human tumors could be a marker of chemotherapy refraction.

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Section: Discussionmentioning

confidence: 99%

Section: Mageb2 Belongs To the Melanoma Antigen Gene (Mage-i)mentioning

confidence: 99%

Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress

Peche

Ladelfa

Toledo

et al. 2015

Journal of Biological Chemistry

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“…Studies on MAGE-A protein function started a decade later. Nowadays, growing body of evidence reported by our and other groups suggest that MAGE-A expression might actively contribute to oncogenesis and refraction to chemotherapy [5]. Consistently, clinical observation indicates a correlation between MAGE-A gene expression and poor prognosis [6,7].…”

Section: Introductionmentioning

confidence: 86%

Functional interaction between co-expressed MAGE-A proteins

et al. 2017

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MAGE-A (Melanoma Antigen Genes-A) are tumor-associated proteins with expression in a broad spectrum of human tumors and normal germ cells. MAGE-A gene expression and function are being increasingly investigated to better understand the mechanisms by which MAGE proteins collaborate in tumorigenesis and whether their detection could be useful for disease prognosis purposes. Alterations in epigenetic mechanisms involved in MAGE gene silencing cause their frequent co-expression in tumor cells. Here, we have analyzed the effect of MAGE-A gene co-expression and our results suggest that MageA6 can potentiate the androgen receptor (AR) co-activation function of MageA11. Database search confirmed that MageA11 and MageA6 are co-expressed in human prostate cancer samples. We demonstrate that MageA6 and MageA11 form a protein complex resulting in the stabilization of MageA11 and consequently the enhancement of AR activity. The mechanism involves association of the Mage A6-MHD domain to MageA11, prevention of MageA11 ubiquitinylation on lysines 240 and 245 and decreased proteasome-dependent degradation. We experimentally demonstrate here for the first time that two MAGE-A proteins can act together in a non-redundant way to potentiate a specific oncogenic function. Overall, our results highlight the complexity of the MAGE gene networking in regulating cancer cell behavior.

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“…7,18,43 Interestingly, MAGE gene expression may protect tumor cells from apoptosis by interfering with p53 activity. 44 SSX2 expression has been described in melanoma, multiple myeloma, and various carcinomas and sarcomas, including gene expression in liposarcomas. 7,18,45 ACRBP mRNA has been detected in various cancers, including bladder, breast, lung, liver, and colon, and protein expression was reported in a majority of epithelial ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma

et al. 2014

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Myxoid and round-cell liposarcoma is a frequently encountered liposarcoma subtype. The mainstay of treatment remains surgical excision with or without chemoradiation. However, treatment options are limited in the setting of metastatic disease. Cancer-testis antigens are immunogenic antigens with the expression largely restricted to testicular germ cells and various malignancies, making them attractive targets for cancer immunotherapy. Gene expression studies have reported the expression of various cancer-testis antigens in liposarcoma, with mRNA expression of CTAG1B, CTAG2, MAGEA9, and PRAME described specifically in myxoid and round-cell liposarcoma. Herein, we further explore the expression of the cancer-testis antigens MAGEA1, ACRBP, PRAME, and SSX2 in myxoid and round-cell liposarcoma by immunohistochemistry in addition to determining mRNA levels of CTAG2 (LAGE-1), PRAME, and MAGEA3 by quantitative real-time PCR. Samples in formalin-fixed paraffin-embedded blocks (n=37) and frozen tissue (n=8) were obtained for immunohistochemistry and quantitative real-time PCR, respectively. Full sections were stained with antibodies to MAGEA1, ACRBP, PRAME, and SSX2 and staining was assessed for intensity (1–2+) and percent tumor positivity. The gene expression levels of CTAG2, PRAME, and MAGEA3 were measured by quantitative real-time PCR. In total, 37/37 (100%) of the samples showed predominantly strong, homogenous immunoreactivity for PRAME. There was a variable, focal expression of MAGEA1 (11%) and SSX2 (16%) and no expression of ACRBP. Quantitative real-time PCR demonstrated PRAME and CTAG2 transcripts in all eight samples: six tumors with high mRNA levels; two tumors with low mRNA levels. The gene expression of MAGEA3 was not detected in the majority of cases. In conclusion, myxoid and round-cell liposarcomas consistently express PRAME by immunohistochemistry as well as CTAG2 and PRAME by qualitative real-time PCR. This supports the use of cancer-testis antigen-targeted immunotherapy in the treatment of this malignancy.

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Tumor-specific MAGE proteins as regulators of p53 function

Cited by 35 publications

References 69 publications

Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress

Human MageB2 Protein Expression Enhances E2F Transcriptional Activity, Cell Proliferation, and Resistance to Ribotoxic Stress

Functional interaction between co-expressed MAGE-A proteins

Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma

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