title: Effects of CT-Xp gene knock down in melanoma cell lines.
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.
authors.affiliation: Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, USA. ocaball1@jhmi.edu
authors.forename: Otavia L
authors.initials: OL
authors.lastname: Caballero
authors.forename: Tzeela
authors.initials: T
authors.lastname: Cohen
authors.forename: Sita
authors.initials: S
authors.lastname: Gurung
authors.forename: Ramon
authors.initials: R
authors.lastname: Chua
authors.forename: Peishan
authors.initials: P
authors.lastname: Lee
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Parmjit
authors.initials: P
authors.lastname: Jat
authors.forename: Andrew J G
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D050172:Genes, X-Linked / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C413656:XAGE1A protein, human; C093962:synovial sarcoma X breakpoint proteins