Insulin-like growth factor-1 receptors and insulin-like growth factor-1-like activity in human primary breast cancer.
In the current study the authors have investigated whether human primary breast cancer specimens contain insulin-like growth factor-1 (IGF-1) receptors (IGF-1-R) or IGF-1-like activities. Simultaneously, epidermal growth factor (EGF) receptors (EGF-R) and cytosolic estrogen receptor (ER), progesterone receptor (PR), and EGF-like activity were determined. All tumors assayed contained a single class of specific iodine 125 (125I)-IGF-1 binding sites (Kd: median 106, range 48-755 pM; n = 32) with limited capacity (Bmax: median 147, range 19-11,900 fmol/mg membrane protein). Seventy percent of 44 tumors (50% ER+, PR+), displayed specific 125I-EGF binding with a wide range of values (median 13, range 2-215 fmol/mg protein, n = 31). A positive relationship was apparent between the amount of IGF-1-R with ER and PR (Spearman; 2P less than 0.02 and 2P less than 0.01, respectively; n = 32), whereas for EGF-R a negative relationship was observed (for both 2P less than 0.01; n = 44). All tumors contained endogeneous IGF-1-like and EGF-like activities as measured by radioreceptor assay on acid-ethanol extracted cytosols (median 15, range 3-131 ng/mg protein, n = 78 for IGF-1; and median 86, range 26-517 ng/mg protein, n = 142 for EGF). Tumor contents of IGF-1-like and EGF-like activities showed a negative relationship with ER (2P less than 0.1 for IGF-1, n = 78; and 2P less than 0.001 for EGF, n = 142), and with PR (2P less than 0.05, n = 78; and 2P less than 0.001, n = 142). No relationship was observed between the tumor contents of IGF-1-like and EGF-like activities. In conclusion, these data support the view that IGF-1 and EGF can act as autocrine or paracrine growth factors in human breast cancer.
Foekens
J A
JA
Division of Endocrine Oncology, Rotterdam Cancer Institute, Dr. Daniel den Hoed Cancer Center, The Netherlands.
Portengen
H
H
Janssen
M
M
Klijn
J G
JG
D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011863:Radioimmunoassay; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017451:Receptors, Somatomedin; D013002:Somatomedins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors