c-erbB2 and c-myb induce mouse oocyte maturation involving activation of maturation promoting factor

DNA Cell Biol. 2012 Feb;31(2):164-70. doi: 10.1089/dna.2011.1219. Epub 2011 Jul 27.

Abstract

Proto-oncogenes are involved in cell growth, proliferation, and differentiation. In the present study, we investigated the roles and mediating pathways of proto-oncogenes c-erbB(2) and c-myb in mouse oocyte maturation by RT-PCR, real-time quantitative PCR, western blot, and recombinant proto-oncogene protein microinjection. Results showed that both c-erbB(2) and c-myb antisense oligodeoxynucleotides (c-erbB(2) ASODN and c-myb ASODN) inhibited germinal vesicle breakdown and the first polar body extrusion in a dose-dependent manner. However, microinjection of recombinant c-erbB(2) or c-myb protein into germinal vesicle stage oocytes stimulated oocyte meiotic maturation. In addition, the expression of c-erbB(2) and c-myb mRNA was detected in oocytes; and c-erbB(2) ASODN and c-myb ASODN inhibited c-erbB(2) mRNA and c-myb mRNA expression, respectively. Maturation promoting factor (MPF) inhibitor roscovitine did not affect the expression of c-erbB(2) mRNA and c-myb mRNA, but blocked the effects of recombinant c-erbB(2) and c-myb protein-induced oocyte maturation. Further, cyclin B1 protein expression in oocytes was remarkably inhibited by c-erbB(2) ASODN, c-myb ASODN, and roscovitine. Nonsense tat ODN had no effect on the expression of c-erbB(2), c-myb, and cyclin B1. These results suggest that c-erbB(2) and c-myb may induce oocyte maturation through mediating a pathway involving the activation of MPF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genes, erbB-2 / drug effects
  • Genes, erbB-2 / genetics
  • Genes, erbB-2 / physiology*
  • Genes, myb / drug effects
  • Genes, myb / genetics
  • Genes, myb / physiology*
  • Maturation-Promoting Factor / genetics*
  • Maturation-Promoting Factor / metabolism
  • Mesothelin
  • Mice
  • Microinjections
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Oocytes / physiology*
  • Oogenesis / drug effects
  • Oogenesis / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-myb / administration & dosage
  • Proto-Oncogene Proteins c-myb / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism
  • Purines / pharmacology
  • Receptor, ErbB-2 / administration & dosage
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Roscovitine
  • Transcriptional Activation

Substances

  • Msln protein, mouse
  • Oligodeoxyribonucleotides, Antisense
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-myb
  • Purines
  • Roscovitine
  • Receptor, ErbB-2
  • Maturation-Promoting Factor
  • Mesothelin