Characterization and quantitation of the epidermal growth factor receptor in invasive and superficial bladder tumors.
Epidermal growth factor receptors (EGFr) have been measured on primary human bladder tumor membranes by 125I-EGF ligand binding. High affinity receptors were detected on both superficial (Kd 0.2-1.45 nM; mean, 0.86 nM; median, 0.88 nM) and invasive tumors (Kd 0.19-2.38 nM; mean, 0.9 nM, median, 0.79 nM). There was one class of binding sites and EGFr concentration was quantified by competitive binding and Scatchard analysis. The EGFr was further characterized and shown to be cleaved at the major autophosphorylation site by a calcium-activated mechanism. Thus the EGFr from primary bladder tumors exhibits similar biochemical characteristics to those in established cell lines. Tumors classified as invasive on the basis of muscle invasion had higher EGFr levels [EGF binding, 99 +/- 252 (SD) fmol/mg protein; median, 21; n = 24] than superficial tumors (12 +/- 12 fmol/mg protein; median, 11; n = 23) or normal bladder mucosa (9 +/- 12 fmol/mg protein; median, 6; n = 6) (P = 0.05). When the two largest subgroups of superficial and invasive tumors were compared (15 pTa, 16 T3), the invasive tumors had significantly higher EGFr levels (P less than 0.05). EGFr may therefore be involved in mechanisms of tumor progression. EGFr may be a target for selective therapy with EGF-linked drugs in a subset of invasive bladder cancers.
Smith
K
K
Department of Clinical Oncology, University of Newcastle upon Tyne, England.
Fennelly
J A
JA
Neal
D E
DE
Hall
R R
RR
Harris
A L
AL
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D001749:Urinary Bladder Neoplasms / Q000032:analysis* / Q000473:pathology
D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors