title: Levels of histone acetylation in thyroid tumors.
abstract: Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness. By using immunohistochemistry we show that acetylated levels of lysines at positions 9-14 of H3 histone (H3K9-K14ac) are significantly higher in follicular adenomas (FA), papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and undifferentiated carcinomas (UC) than in normal tissues (NT). Similar data have been obtained when acetylated levels of lysine 18 of H3 histone (H3K18ac) were evaluated. In this case, however, no difference was observed between NT and UC. When acetylated levels of lysine 12 of H4 histone (H4K12ac) were evaluated, only FA showed significantly higher levels in comparison with NT. These data indicate that modification histone acetylation is an early event along thyroid tumor progression and that H3K18 acetylation is switched off in the transition between differentiated and undifferentiated thyroid tumors. By using rat thyroid cell lines that are stably transfected with doxycyclin-inducible oncogenes, we show that the oncoproteins RET-PTC, RAS and BRAF increase levels of H3K9-K14ac and H3K18ac. In the non-tumorigenic rat thyroid cell line FRTL-5, TSH increases levels of H3K18ac. However, this hormone decreases levels of H3K9-K14ac and H4K12ac. In conclusion, our data indicate that neoplastic transformation and hormonal stimulation can modify levels of histone acetylation in thyroid cells.
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Nadia
authors.initials: N
authors.lastname: Passon
authors.forename: Elisa
authors.initials: E
authors.lastname: Lavarone
authors.forename: Carla
authors.initials: C
authors.lastname: Di Loreto
authors.forename: Francesco
authors.initials: F
authors.lastname: Frasca
authors.forename: Veronica
authors.initials: V
authors.lastname: Vella
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vigneri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D051381:Rats; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D006657:Histones