Melanoma-associated cancer-testis antigen 16 (CT16) regulates the expression of apoptotic and antiapoptotic genes and promotes cell survival

Cancer-testis (CT) antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5) is frequently expressed in advanced melanoma but its biological function has been unknown. To exa...

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Bibliographic Details
Published in:PloS one 2012-09, Vol.7 (9), p.e45382-e45382
Main Authors: Nylund, Camilla, Rappu, Pekka, Pakula, Eveliina, Heino, Aleksi, Laato, Laura, Elo, Laura L, Vihinen, Pia, Pyrhönen, Seppo, Owen, Gethin R, Larjava, Hannu, Kallajoki, Markku, Heino, Jyrki
Format: Article
Language:English
Subjects:
Antigens
Apoptosis
Apoptosis - genetics
Apoptosis - physiology
Biochemistry
Bioinformatics
Biology
Blotting, Western
Cancer
Cell Line, Tumor
Cell Proliferation
Cell survival
Cell Survival - genetics
Cell Survival - physiology
Cisplatin
Deoxyribonucleic acid
Dkk1 protein
DNA
DNA methylation
Drug development
Fatty acid-binding protein
Fatty acids
Food
Gene expression
Genes
Genetic transformation
Humans
Immunohistochemistry
In Vitro Techniques
Interleukin 8
Kinases
Medicine
Melanoma
Melanoma - genetics
Melanoma - metabolism
Melanoma-Specific Antigens - genetics
Melanoma-Specific Antigens - metabolism
Metallothionein
Metastases
Metastasis
p53 Protein
Placenta
Promoter Regions, Genetic - genetics
Prostate cancer
Proteins
Radiation therapy
Real-Time Polymerase Chain Reaction
siRNA
Skin cancer
Survival
Tissues
Transformation
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumorigenesis
Tumors
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Summary:Cancer-testis (CT) antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5) is frequently expressed in advanced melanoma but its biological function has been unknown. To examine the role of CT16 in cell survival we knocked it down in A2058 melanoma cells using specific siRNAs and exposed the cells to cancer drug cisplatin known to induce apoptosis. As a result, cell survival was markedly decreased. To study the effects of CT16 on cell survival in more detail, the cellular gene expression profiles were investigated after CT16 silencing in CT16 positive A2058 melanoma cells, as well as after CT16 overexpression in CT16 negative WM-266-4 melanoma cells. Among the 11 genes both upregulated by CT16 silencing and downregulated by CT16 overexpression or vice versa, 4 genes were potentially apoptotic or antiapoptotic genes. CT16 was recognized as a positive regulator of antiapoptotic metallothionein 2A and interleukin 8 genes, whereas it inhibited the expression of apoptosis inducing dickkopf 1 (DKK1) gene. In addition CT16 enhanced the expression of fatty acid binding protein 7, a known promoter of melanoma progression. The effect of CT16 on DKK1 expression was p53 independent. Furthermore, CT16 did not regulate apoptotic genes via DNA methylation. In twenty melanoma metastasis tissue samples average DKK1 mRNA level was shown to be significantly (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0045382