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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.

Type

Journal article

Journal

Cancer Res

Publication Date

01/11/1989

Volume

49

Pages

5810 - 5815

Keywords

Aged, Biomarkers, Tumor, Cell Membrane, Epidermal Growth Factor, Female, Humans, Kinetics, Male, Molecular Weight, Neoplasm Invasiveness, Neoplasm Metastasis, Receptor, Epidermal Growth Factor, Urinary Bladder Neoplasms