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Insulin-like growth factors in human breast cancer
1Lombardi Cancer Research Center, Georgetown University Medical Center, Washington DC.
Abstract:
Several protooncogenes and suppressor genes and a variety of growth factors and their receptors have been shown to be mutated, deleted, or activated in human breast cancer. These changes may account for the unregulated growth of breast carcinoma cells. Insulin-like growth factors I and II (IGF-I, IGF-II) belong to a family of polypeptides with growth promoting properties and structural homology to insulin. They exert their mitogenic effects by binding to the IGF-I receptor and activating its tyrosine protein kinase. Other proteins that specifically bind the IGFs include the plasma membrane IGF-II receptor, which also binds lysosomal hydrolases, and several IGF-binding proteins which may serve to modulate IGF interactions with receptors. Breast cancer cell lines express IGF-I and IGF-II receptors and different patterns of binding proteins. IGF-I and IGF-II are each mitogenic for subsets of breast cancer cell lines. This effect is inhibited by antibodies directed against the IGF-I receptor. In breast tumors, IGF-I is expressed by stromal cells, but not carcinoma cells; it is not expressed by breast cancer cell lines. IGF-I is therefore a potential paracrine regulator of breast cancer cell growth. Similarly, IGF-II is expressed in breast tumors, predominantly in stromal cells, but sometimes also in carcinoma cells and in a subset of cell lines. Thus, IGF-II is also a potential paracrine regulator of breast cancer cell growth; in addition, it can be an autocrine regulator in some breast cancer cells.
Insights
Insulin-like growth factors I and II (IGF-I, IGF-II) promote breast cancer cell growth by activating specific receptors. These factors may act as paracrine or autocrine regulators in breast tumors.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Human breast cancer involves genetic alterations in protooncogenes and suppressor genes, leading to unregulated cell growth.
- Insulin-like growth factors I and II (IGF-I, IGF-II) are mitogenic polypeptides that bind to the IGF-I receptor, activating its tyrosine kinase activity.
Purpose of the Study:
- To investigate the role of IGF-I and IGF-II in breast cancer cell proliferation.
- To determine the expression patterns and regulatory functions of IGFs and their receptors in breast tumors and cell lines.
Main Methods:
- Analysis of IGF-I and IGF-II receptor expression and binding protein patterns in breast cancer cell lines.
- Assessment of the mitogenic effects of IGF-I and IGF-II on breast cancer cell lines, and the impact of IGF-I receptor antibodies.
- Evaluation of IGF-I and IGF-II expression in breast tumors and cell lines.
Main Results:
- Breast cancer cell lines express IGF-I and IGF-II receptors and various binding proteins.
- IGF-I and IGF-II exhibit mitogenic effects on distinct subsets of breast cancer cell lines, which can be blocked by IGF-I receptor antibodies.
- IGF-I is primarily expressed by stromal cells in breast tumors, suggesting paracrine regulation, while IGF-II is found in stromal and sometimes carcinoma cells, indicating both paracrine and autocrine potential.
Conclusions:
- IGF-I and IGF-II play significant roles in regulating breast cancer cell growth.
- IGF-I acts as a potential paracrine regulator, whereas IGF-II can function as both a paracrine and autocrine regulator in breast cancer.