Elevated insulin-like growth factor I receptor autophosphorylation and kinase activity in human breast cancer

Insulin-like growth factor I action has been implicated in the pathogenesis of many different malignancies, including breast cancer. Insulin-like growth factor I receptors (IGF-IRs) are overexpressed in virtually all breast cancer cell lines, in which they are believed to enhance growth and inhibit...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-03, Vol.58 (6), p.1159-1164
Main Authors: RESNIK, J. L, REICHART, D. B, KIM HUEY, WEBSTER, N. J. G, SEELY, B. L
Format: Article
Language:English
Subjects:
Biological and medical sciences
Breast - enzymology
Breast Neoplasms - enzymology
Gynecology. Andrology. Obstetrics
Humans
Ligands
Mammary gland diseases
Medical sciences
Phosphorylation
Phosphotyrosine - metabolism
Protein Tyrosine Phosphatases - metabolism
Receptor Protein-Tyrosine Kinases - metabolism
Receptor, Insulin - metabolism
Receptors, Somatomedin - metabolism
Tumors
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Summary:Insulin-like growth factor I action has been implicated in the pathogenesis of many different malignancies, including breast cancer. Insulin-like growth factor I receptors (IGF-IRs) are overexpressed in virtually all breast cancer cell lines, in which they are believed to enhance growth and inhibit apoptosis. In this study, the functional activity of IGF-IRs from normal and malignant human breast tissue was assessed. IGF-IR expression was 14-fold higher in malignant breast tissue than in normal breast tissue. IGF-IR autophosphorylation and kinase activity were 2-4-fold higher in purified receptor preparations from malignant breast tissue as compared to normal breast tissue when normalized for receptor number. This increase in receptor function, coupled with the enhanced receptor expression, amounts to a 40-fold elevation in IGF-IR tyrosine kinase activity in malignant breast tissue. The enhanced receptor autophosphorylation and kinase activity were observed in the absence of hormonal stimulation and seem to result from an alteration in the intrinsic activity of the receptor itself. Protein tyrosine phosphatase activity is also increased in malignant breast tissue. These data suggest that the IGF-IR is an important target for breast cancer therapy.
ISSN:0008-5472
1538-7445