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Type of publication: Journal Article
Type of document: Full Paper

Year: 2010

Authors: Lagger, S; Meunier, D; Mikula, M; Brunmeir, R; Schlederer, M; Artaker, M; Pusch, O; Egger, G; Hagelkruys, A; Mikulits, W; Weitzer, G; Muellner, EW; Susani, M; Kenner, L; Seiser, C

Title: Crucial function of histone deacetylase 1 for differentiation of teratomas in mice and humans.

Source: Embo J. 2010; 29(23):3992-4007



Authors Vetmeduni Vienna:

Kenner Lukas
Lagger Sabine


Abstract:
Histone deacetylase (HDAC) inhibitors induce cell cycle arrest, differentiation or apoptosis in tumour cells and are, therefore, promising anti-cancer reagents. However, the specific HDAC isoforms that mediate these effects are not yet identified. To explore the role of HDAC1 in tumourigenesis and tumour proliferation, we established an experimental teratoma model using wild-type and HDAC1-deficient embryonic stem cells. HDAC1-deficient teratomas showed no significant difference in size compared with wild-type teratomas. Surprisingly, loss of HDAC1 was not only linked to increased apoptosis, but also to significantly enhanced proliferation. Epithelial structures showed reduced differentiation as monitored by Oct3/4 expression and changed E-cadherin localization and displayed up-regulated expression of SNAIL1, a regulator of epithelial cell plasticity. Increased levels of the transcriptional regulator SNAIL1 are crucial for enhanced proliferation and reduced differentiation of HDAC1-deficient teratoma. Importantly, the analysis of human teratomas revealed a similar link between loss of HDAC1 and enhanced tumour malignancy. These findings reveal a novel role for HDAC1 in the control of tumour proliferation and identify HDAC1 as potential marker for benign teratomas.

Keywords Pubmed: Animals
Apoptosis
Cadherins/genetics
Carcinoma, Embryonal/enzymology
Carcinoma, Embryonal/genetics
Carcinoma, Embryonal/pathology
Cell Line
Cell Line, Tumor
Cell Proliferation
Embryonic Stem Cells/cytology
Embryonic Stem Cells/metabolism*
Embryonic Stem Cells/pathology
Gene Expression Regulation, Neoplastic*
Histone Deacetylase 1/genetics*
Histone Deacetylase 1/metabolism
Humans
Mice
Octamer Transcription Factor-3/genetics
Phenotype
Teratoma/enzymology*
Teratoma/genetics
Teratoma/pathology
Transcription Factors/genetics


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