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 pathoge nesis of many different malignancies, including breast cancer. Insulin -like growth factor I receptors (IGF-IRs) are overexpressed in virtual ly 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 I l-fold higher in malignant breast tissue than in normal breast tissue. IGF-IR autophosphorylation and kinase activit y were 2-4-fold higher in purified receptor preparations from malignan t breast tissue as compared to normal breast tissue when normalized fo r receptor number. This increase in receptor function. coupled with th e enhanced receptor expression, amounts to a 40-fold elevation in IGF- W tyrosine kinase activity in malignant breast tissue. The enhanced re ceptor autophosphorylation and kinase activity were observed in the ab sence of hormonal stimulation and seem to result from an alteration in the intrinsic activity of the receptor itself. Protein tyrosine phosp hatase activity is also increased in malignant breast tissue. These da ta suggest that the IGF-IR is an important target for breast cancer th erapy.