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Minireview: physiological and pathological actions of RAS in the ovary

Heng-Yu Fan1, Joanne S Richards

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. joanner@bcm.edu.

Molecular Endocrinology (Baltimore, Md.)
|November 3, 2009
PubMed

Insights

RAS proteins are vital for ovarian function and ovulation. Aberrant RAS signaling, particularly KRAS mutations, disrupts follicular development and can lead to ovarian cancers, offering insights into human ovarian diseases.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Reproductive Biology

Background:

  • RAS superfamily proteins act as molecular switches in cellular signal transduction.
  • RAS gene functions in ovarian cells are beginning to be understood.
  • KRAS is highly expressed in granulosa cells and is implicated in ovulation.

Purpose of the Study:

  • To summarize the physiological and pathological roles of RAS in the rodent ovary.
  • To discuss implications of Kras(G12D) mutant mouse models for human ovarian diseases.
  • To highlight new research questions regarding RAS in ovarian function and pathology.

Main Methods:

  • Conditional expression of constitutively active Kras(G12D) mutant in granulosa cells.
  • Disruption of the tumor suppressor Pten in Kras(G12D)-expressing granulosa cells.
  • Analysis of ovarian surface epithelial cells with Pten;Kras(G12D) mutations.

Main Results:

  • Kras(G12D) expression in granulosa cells disrupts follicular growth, proliferation, apoptosis, and differentiation, leading to ovulation defects.
  • Disruption of Pten in Kras(G12D)-expressing granulosa cells prevents granulosa cell tumor development.
  • Ovarian surface epithelial cells with Pten;Kras(G12D) mutations rapidly develop serous cystadenocarcinomas.

Conclusions:

  • RAS signaling is crucial for normal ovarian physiology, particularly ovulation.
  • Aberrant RAS signaling, especially KRAS mutations, contributes to ovarian pathologies, including cancer.
  • Kras(G12D) mouse models provide valuable insights into human premature ovarian failure and ovarian cancers.

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