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Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced

B Schnarr1, K Strunz, J Ohsam

  • 1Hormones and Signal Transduction Research Group, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

International Journal of Cancer
|December 5, 2000
PubMed

Insights

Insulin-like growth factor-I receptor (IGF-IR) and insulin receptor substrate-1 (IRS-1) expression decreases as breast cancer progresses. Down-regulation of IGF-IR and IRS-1 correlates with tumor grade, suggesting their use as novel breast cancer markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Insulin-like growth factor (IGF) family signaling pathways regulate breast cancer cell growth.
  • Key components include IGF-I receptor (IGF-IR), insulin receptor (IR), and IRS-1.

Purpose of the Study:

  • To investigate the expression patterns of IGF-IR, IR, and IRS-1 in primary breast cancer tissues.
  • To correlate their expression with tumor grade, cell proliferation (Ki67), and estrogen receptor (ER) status.

Main Methods:

  • Immunohistochemistry was used to assess protein expression in 69 primary breast cancer specimens and 21 control tissues.
  • Cell proliferation and ER expression were also determined.

Main Results:

  • IGF-IR and IRS-1 were highly expressed in normal tissues and well-differentiated tumors, but lowly expressed in poorly differentiated cancers.
  • IR expression did not significantly correlate with tumor grade.
  • Down-regulation of IGF-IR and IRS-1 showed a stronger correlation with tumor progression than ER expression or Ki67 levels.

Conclusions:

  • Breast cancer progression is associated with reduced IGF-IR and IRS-1 expression.
  • IGF-IR and IRS-1 expression inversely correlates with proliferation in dedifferentiated breast cancers.
  • IGF-IR and IRS-1 show potential as novel biomarkers for breast cancer grading.

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