A set of imprinted genes required for normal body growth also promotes growth of rhabdomyosarcoma cells

Pediatr Res. 2012 Jan;71(1):32-8. doi: 10.1038/pr.2011.6.

Abstract

Introduction: In many normal tissues, proliferation rates decline postnatally, causing somatic growth to slow. Previous evidence suggests that this decline is due, in part, to decline in the expression of growth-promoting imprinted genes including Mest, Plagl1, Peg3, Dlk1, and Igf2. Embryonal cancers are composed of cells that maintain embryonic characteristics and proliferate rapidly in childhood. We hypothesized that the abnormal persistent rapid proliferation in embryonal cancers occurs in part because of abnormal persistent high expression of growth-promoting imprinted genes.

Results: Analysis of microarray data showed elevated expression of MEST, PLAGL1, PEG3, DLK1, and IGF2 in various embryonal cancers, especially rhabdomyosarcoma, as compared to nonembryonal cancers and normal tissues. Similarly, mRNA expression, assessed by real-time PCR, of MEST, PEG3, and IGF2 in rhabdomyosarcoma cell lines was increased as compared to nonembryonal cancer cell lines. Furthermore, siRNA-mediated knockdown of MEST, PLAGL1, PEG3, and IGF2 expression inhibited proliferation in Rh30 rhabdomyosarcoma cells.

Discussion: These findings suggest that the normal postnatal downregulation of growth-promoting imprinted genes fails to occur in some embryonal cancers, particularly rhabdomyosarcoma, and contributes to the persistent rapid proliferation of rhabdomyosarcoma cells and, more generally, that failure of the mechanisms responsible for normal somatic growth deceleration can promote tumorigenesis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Child
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Genomic Imprinting*
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Microarray Analysis
  • Proteins / genetics
  • Proteins / metabolism
  • Rhabdomyosarcoma / genetics*
  • Rhabdomyosarcoma / pathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Kruppel-Like Transcription Factors
  • PEG3 protein, human
  • PLAGL1 protein, human
  • Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • mesoderm specific transcript protein
  • Insulin-Like Growth Factor II