title: Acetylated Sp1 inhibits PTEN expression through binding to PTEN core promoter and recruitment of HDAC1 and promotes cancer cell migration and invasion.
abstract: Specificity protein 1 (Sp1) is often overexpressed in cancer cells. Its binding sites are known to exist in the phosphatase and tension homolog deleted on chromosome 10 (PTEN) promoter. In this study, we hypothesized that Sp1 negatively regulates PTEN expression. We used several cell lines to determine the effects of Sp1. The results showed that Sp1 overexpression inhibited the expression and promoter activity of PTEN and correspondingly upregulated AKT phosphorylation, whereas Sp1 knockdown upregulated the expression and promoter ability of PTEN and downregulated AKT phosphorylation. Moreover, a series of deletion and site-directed mutations of the PTEN promoter indicated that Sp1 can inhibit PTEN promoter activity through a specific Sp1-binding site at the PTEN core promoter in vivo. Meanwhile, non-acetylated Sp1, with its loss of DNA binding activity, failed to inhibit the expression and promoter activity of PTEN. Histone deacetylase 1 was necessary for Sp1 to inhibit PTEN expression. The inverse expression of Sp1 and PTEN was found in tongue cancer cells and salivary adenoid cystic cancer (SACC)-LM cells (possessing higher potential for lung metastasis than SACC-83) as compared with that in adjacent normal tissue and SACC-83 cells, respectively. Sp1 knockdown decreased the migration and invasion of SACC-LM cells, whereas Sp1 overexpression increased the migration and invasion of SACC-83 cells. Overall, these results suggest that Sp1 is involved in the development and invasiveness of cancer through inhibition of PTEN.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Kou
authors.forename: Ting
authors.initials: T
authors.lastname: Hao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Meng
authors.forename: Yan-Heng
authors.initials: YH
authors.lastname: Zhou
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D016329:Sp1 Transcription Factor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D056284:Histone Deacetylase 1