Cytoplasmic localization of EGF receptor in papillary thyroid carcinomas: association with the 150-kDa receptor form.
We have previously reported that papillary thyroid carcinomas show an increased expression of EGFR mRNA and protein, compared to non-tumorous thyroid tissue. EGFR immunoreactivity was localized to the cytoplasm as well as to the membrane in papillary carcinomas. To further study EGFR protein expression in human thyroid tissue, we performed immunohistochemistry and Western blots of 64 different thyroid tissue samples from 36 patients, including 23 patients with papillary carcinomas. Two receptor forms were identified in human thyroid tissue, a 170-kDa and a 150-kDa form. The 150-kDa receptor form was more pronounced in papillary carcinomas, while the 170-kDa receptor was the dominant form in non-malignant thyroid tissues. Predominance of the 150-kDa EGFR in the tumour samples was associated with strong cytoplasmic EGFR staining. EGFR gene structure, protein synthesis and maturation were found to be normal. Immunoprecipitation and Western-blot analysis of EGFR from the human thyroid SGHTL-34 cells after increased ligand concentration showed a decreased amount of the mature 170-kDa receptor and a relative increase in the 150-kDa receptor. We have previously demonstrated the presence of a TGF-alpha-EGFR autocrine loop in papillary thyroid carcinomas, and this may explain increased receptor turnover and accumulation of a cytoplasmic degradation product.
Ness
G O
GO
Department of Biochemistry and Molecular Biology, Grade Institute, University of Bergen, Norway.
Haugen
D R
DR
Varhaug
J E
JE
Akslen
L A
LA
Lillehaug
J R
JR
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D066246:ErbB Receptors