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Insulin-like growth factor receptor expression and function in human breast cancer
1Vincent T. Lombardi Cancer Research Center, Georgetown University, Washington, DC 20007.
Cancer Research
|January 1, 1990
Summary
Insulin-like growth factors (IGF-I and IGF-II) promote breast tumor cell growth. Research indicates these effects are primarily mediated through the type I IGF receptor, which is common in breast cancers.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Insulin-like growth factors (IGF-I and IGF-II) are known mitogens for breast tumor cells.
- While IGF mRNAs are detected in tumors, their expression in breast cancer cell lines is limited.
- Receptor cross-reactivity within the insulin/IGF family complicates understanding their specific roles in breast cancer.
Purpose of the Study:
- To investigate the expression of type I and type II IGF receptors and insulin receptor mRNAs in breast tumor specimens and cell lines.
- To determine which IGF receptor mediates the mitogenic effects of IGF-I and IGF-II in breast cancer cells.
Main Methods:
- RNase protection assay to analyze mRNA expression of IGF receptors and insulin receptor.
- Mitogenic assays using estrogen-dependent MCF-7 cells treated with IGF-I, IGF-II, and insulin.
- Utilized monoclonal antibody alpha IR-3 to block the type I IGF receptor.
Main Results:
- All examined breast tumor specimens and cell lines expressed mRNA for type I and type II IGF receptors and the insulin receptor.
- Antibody alpha IR-3 blocked the mitogenic effects of both IGF-I and IGF-II in MCF-7 cells.
- Insulin's mitogenic effects were not blocked by alpha IR-3, indicating receptor specificity.
Conclusions:
- Type I and type II IGF receptors are ubiquitously expressed in breast cancer.
- The mitogenic effects of both IGF-I and IGF-II in breast cancer cells are primarily mediated by the type I IGF receptor.