Consequences of RAS and MAPK Activation in the Ovary: The Good, the Bad and the Ugly

Mol Cell Endocrinol. 2012 Jun 5;356(1-2):74-9. doi: 10.1016/j.mce.2011.12.005. Epub 2011 Dec 16.


This review summarizes studies providing evidence (1) that endogenous RAS activation regulates important physiological events during ovulation and luteinization (2) that expression of the mutant, active KRAS(G12D) in granulosa cells in vivo causes abnormal follicle growth arrest leading to premature ovarian failure and (3) that KRAS(G12D) expression in ovarian surface epithelial (OSE) cells renders them susceptible to the pathological outcome of transformation and tumor formation. These diverse effects of RAS highlight how critical its activation is linked to cell- and stage-specific events in the ovary that control normal processes and that can also lead to altered granulosa cell and OSE cell fates.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial
  • Enzyme Activation*
  • Female
  • Granulosa Cells / enzymology
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutation, Missense
  • Neoplasms, Glandular and Epithelial / enzymology
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics
  • Ovary / enzymology*
  • Ovulation
  • ras Proteins / genetics
  • ras Proteins / metabolism*
  • ras Proteins / physiology


  • Mitogen-Activated Protein Kinases
  • ras Proteins