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Epidermal growth fa...
Epidermal growth factor receptor signaling activates Met in human anaplastic thyroid carcinoma cells
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- Bergström, J.Daniel (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Westermark, Bengt (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Heldin, Nils-Erik (author)
- Uppsala universitet,Institutionen för genetik och patologi
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(creator_code:org_t)
- Elsevier BV, 2000
- 2000
- English.
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In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 259:1, s. 293-299
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Overexpression of Met is a common finding in thyroid carcinomas. Recently, we reported on overexpression and ligand-independent constitutive activation of Met in anaplastic thyroid carcinoma cells. In the present study we have investigated a putative mechanism for this phenomenon. Cell lines with constitutively activated Met expressed both TGF-alpha mRNA and protein. Western blot analysis revealed expression of receptors for epidermal growth factor (EGFR) in all carcinoma cell lines; in tumor cells with elevated levels of TGF-alpha mRNA there was a constitutive tyrosine phosphorylation of the EGFRs. Preincubation of carcinoma cells with suramin decreased EGFR activation and downregulated Met expression as well as the ligand-independent phosphorylation of Met. Similar results were obtained with a EGFR tyrosine kinase inhibitor, AG 1478. The MEK inhibitor U0126 had an even more pronounced effect compared to AG 1478, indicating a Ras/MAPK-mediated signal in the regulation of Met expression and activation. Inhibition of EGFR signaling also decreased proliferation of the anaplastic thyroid carcinoma cells. Thus, aberrant activation of EGFRs may lead to an overexpression and activation of Met, which may be of importance for the malignant phenotype of anaplastic thyroid carcinomas.
Keyword
- carcinoma
- EGFR
- Met
- receptor activation
- thyroid
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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