In thyroid cancer cell lines expression of periostin gene is controlled by p73 and is not related to epigenetic marks of active transcription

Cell Oncol (Dordr). 2011 Apr;34(2):131-40. doi: 10.1007/s13402-011-0009-9. Epub 2011 Jan 27.

Abstract

Background: Periostin expression is a feature of the epithelial-mesenchymal transition, which occurs during cancer progression. Previous reports indicate that periostin expression is related to tumour aggressiveness.

Methods: In order to identify mechanisms regulating periostin expression in thyroid cancer, a panel of continuous thyroid cancer cell lines was investigated. Levels of posttranslational modifications of the H3 histone were investigated by chromatin immunoprecipitation. Moreover, treatment of cell lines with deacetylase inhibitors and transfection experiments were performed.

Results: Our insights show that levels of H3 histone acetylated at lysines 9 and 14 (which are epigenetic marks of active transcription) are not related to periostin mRNA levels. Moreover, treatment of WRO and FRO thyroid cancer cell lines with the deacetylase inhibitor tricostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) increases levels of acetylated H3 histone to periostin promoter however, unpredictably, reduces periostin mRNA levels. Interestingly, treatment of WRO cells with either TSA or SAHA increases levels of the H3 histone trimethylated at lysine 4, which is a different epigenetic mark of active transcription. Instead, data obtained by cell transfection indicate that ΔNp73, a member of p53 family selectively expressed in thyroid carcinomas, plays a role in activating periostin gene expression.

Conclusions: Levels of epigenetic marks of active transcription do not contribute to regulation of periostin gene expression. The ΔNp73 effects suggest a novel molecular mechanism involved in thyroid cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Blotting, Western
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • Epigenomics
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Histone Deacetylase Inhibitors / pharmacology
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Lysine / metabolism
  • Mutation
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Protein p73
  • Tumor Suppressor Proteins / genetics*

Substances

  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Nuclear Proteins
  • POSTN protein, human
  • RNA, Messenger
  • TP73 protein, human
  • Transcription Factors
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • delta Np73 protein, human
  • trichostatin A
  • Lysine