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Suppression of mammary-derived growth inhibitor gene expression by growth hormone and insulin-like growth factor I

H Huynh1, W Beamer

  • 1McGill University Centre for Translational Research in Cancer, Lady Davis Research Institute, Montreal, H3T 1E2 Quebec, Canada.

International Journal of Oncology
|July 31, 1998
PubMed

Insights

The mammary-derived growth inhibitor (MDGI) gene, a tumor suppressor, is silenced in breast cancer. Insulin-like growth factor-I (IGF-I) regulates MDGI, offering new avenues for breast cancer prevention and treatment.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • The mammary-derived growth inhibitor (MDGI) gene acts as a tumor suppressor, reverting breast cancer cells to normal behavior.
  • MDGI is frequently silenced in human breast cancer cell lines and tumors.
  • Antiestrogens stabilize MDGI mRNA, suggesting a role in breast cancer therapy.

Purpose of the Study:

  • To investigate the regulatory relationship between Insulin-like Growth Factors (IGFs) and the tumor suppressor gene MDGI.
  • To explore the potential of targeting the IGF axis for breast cancer prevention and treatment.

Main Methods:

  • Gene expression analysis in MCF-7 breast cancer cells and mouse models.
  • Administration of IGF-I, Growth Hormone (GH), and octreotide to assess effects on MDGI expression.
  • Correlation analysis between MDGI and IGF-II gene expression.

Main Results:

  • MDGI gene expression was inversely correlated with IGF-II gene expression.
  • MDGI was overexpressed in the mammary glands of Ghrhrlit/Ghrhrlit mice.
  • IGF-I and GH suppressed MDGI mRNA levels in a dose-dependent manner in mice.
  • Octreotide up-regulated mammary gland MDGI expression in rats.

Conclusions:

  • Insulin-like growth factor-I (IGF-I) plays a significant, previously unrecognized role in regulating the tumor suppressor gene MDGI in the mammary gland.
  • These findings may inform novel physiological strategies for breast cancer prevention and treatment.

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