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Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related

Jennifer H Law1, Golareh Habibi, Kaiji Hu

  • 1Department of Pediatrics, Laboratory for Oncogenomic Research, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Cancer Research
|December 17, 2008
PubMed

Insights

Activated insulin-like growth factor-I receptor (IGF-IR) and insulin receptor (IR) in breast cancer predict poor survival. This activated receptor is present across all subtypes and may be a target for new therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Drugs targeting insulin-like growth factor-I receptor (IGF-IR) and insulin receptor (IR) are under investigation for various cancers, including breast cancer.
  • While IGF-IR expression is common in primary breast tumors, its activation status and correlation with patient survival remain largely unexamined.

Purpose of the Study:

  • To evaluate the activation status of IGF-IR/IR in breast cancer tissues.
  • To determine if the activation status of IGF-IR/IR correlates with patient survival and breast cancer subtypes.
  • To assess the therapeutic potential of IGF-IR/IR inhibitors in preclinical models.

Main Methods:

  • Immunohistochemistry was used to assess phosphorylated IGF-IR/IR (P-IGF-IR/IR) and phospho-S6 (P-S6) in 438 invasive breast cancer tissue microarrays.
  • Correlation of P-IGF-IR/IR and total IR/IGF-IR levels with patient survival was analyzed.
  • The efficacy of the IGF-IR/IR inhibitor BMS-536924 was tested in vitro on various breast cancer cell lines and tamoxifen-resistant cells.

Main Results:

  • Phosphorylated IGF-IR/IR (P-IGF-IR/IR) and total IR levels were associated with poor breast cancer survival (P = 0.046 and P = 0.009, respectively).
  • P-IGF-IR/IR and P-S6 were coordinately expressed and detected in all breast cancer subtypes (luminal, triple-negative, HER2).
  • BMS-536924 suppressed the growth of multiple breast cancer cell lines, including tamoxifen-resistant cells, with minimal effect on normal breast cells.

Conclusions:

  • Activated IGF-IR/IR is a significant prognostic factor for breast cancer, indicating poor survival.
  • The presence of activated IGF-IR/IR across all breast cancer subtypes suggests its potential as a predictive marker for targeted therapies.
  • IGF-IR/IR inhibitors show promise for treating various breast cancer subtypes, including those resistant to tamoxifen.

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