Non-autocrine, constitutive activation of Met in human anaplastic thyroid carcinoma cells in culture.

Abstract:

:Activation of Met by its ligand HGF has been shown to elicit both mitogenic and motogenic responses in thyrocytes in vitro. In the present study we have investigated the expression of Met in human anaplastic thyroid carcinoma cells in culture. There was a variation in expression level and size of Met in the different cell lines; high Met expression was found in four cell lines, compared to non-neoplastic human thyrocytes. Treatment with glucoproteinase F showed that the size differences observed were due to variances in the degree of glycosylation. Interestingly, in cell lines with high expression of Met, the receptor proteins were found to be constitutively tyrosine phosphorylated. None of these cell lines expressed HGF mRNA, and addition of suramin did not affect the level of tyrosine phosphorylation of Met in unstimulated cells, suggesting the absence of autocrine stimulatory pathways. Furthermore, we did not observe MET gene amplification, activating mutations or phosphatase defects. The tyrosine phosphorylated receptors appeared functionally active since the receptors associated with the adaptor molecule Shc. In summary, we have found ligand-independent constitutively activated Met in four out of six anaplastic thyroid carcinoma cell lines.

journal_name

Br J Cancer

authors

Bergström JD,Hermansson A,Diaz de Ståhl T,Heldin NE

doi

10.1038/sj.bjc.6690406

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

650-6

issue

5-6

eissn

0007-0920

issn

1532-1827

journal_volume

80

pub_type

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