Oncotarget

Research Papers:

Effects of CT-Xp Gene Knock down in Melanoma Cell Lines

Otavia Luisa Caballero _, Tzeela Cohen, Sita Gurung, Ramon Chua, Peishan Lee, Yao-Tseng Chen, Parmjit Jat, Lloyd J. Old and Andrew J. G. Simpson

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Oncotarget. 2013; 4:531-541. https://doi.org/10.18632/oncotarget.921

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Abstract

Otavia L. Caballero1*&, Tzeela Cohen1,*, Sita Gurung1, Ramon Chua1, Peishan Lee2, Yao-Tseng Chen2, Parmjit Jat3, Andrew J. G. Simpson4

1 Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, USA

2 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, New York, USA

3 Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK

4 Ludwig Institute for Cancer Research, 666 Third Avenue, New York, NY, USA

* These authors contributed equally to this work.

& Current address: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD

Correspondence:

Otavia L. Caballero, email:

Keywords: Cancer/testis genes, GAGE, XAGE1, SSX, siRNA, melanoma

Received: March 6, 2013 Accepted: March 25, 2013 Published: March 27, 2013

Abstract

Cancer/testis (CT) genes are encoded by genes that are normally expressed only in the human germ line but which are activated in various malignancies. CT proteins are frequently immunogenic in cancer patients and their expression is highly restricted to tumors. They are thus important targets for anticancer immunotherapy. In several different tumor types, the expression of CT-X genes is associated with advanced disease and poor outcome, indicating that their expression might contribute to tumorigenesis. CT-X genes encoding members of the MAGE protein family on Xq28 have been shown to potentially influence the tumorigenic phenotype. We used small interfering RNA (siRNA) to investigate whether CT-X mapping to the short arm of the X-chromosome might also have tumorigenic properties and therefore be potentially targeted by functional inhibitors in a therapeutic setting. siRNAs specific to GAGE, SSX and XAGE1 were used in cell proliferation, migration and cell survival assays using cell lines derived from melanoma, a tumor type known to present high frequencies of expression of CT antigens. We found that of these, those specific to GAGE and XAGE1 most significantly impeded melanoma cell migration and invasion and those specific to SSX4 and XAGE1 decreased the clonogenic survival of melanoma cells. Our results suggest that GAGE, XAGE1 and SSX4 might each have a role in tumor progression and are possible therapeutic targets for the treatment of melanoma and other malignancies.


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