Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl

Protein-tyrosine kinases (PTKs) play a crucial role in regulating thyroid cell growth and differentiation. It is known that PTKs are activated by ionizing radiation, but the critical pathways through ionizing radiation-induced malignant transformation are not well defined. The Axl protein is a member of a new family of Receptor Tyrosine Kinases, which the ligand, Gas6, a protein S-related molecule, has recently been identified. We previously clarified the expression of Axl and mitogenic action of Gas6 in thyroid carcinoma cells. To investigate the involvement of Gas6-Axl signaling in pediatric thyroid carcinoma further, we examined tissues obtained from 17 patients with thyroid papillary carcinomas from Gomel, Belarus, by immunohistochemistry and in situ hybridization. Axl and Gas6 were overexpressed in 76.5% and 70.6 % of cases, respectively. Solid component and invasive front tended to overexppress Gas6 and Axl in papillary carcinomas. Eighty-five percent of Axl positive cases coexpressed Gas6. In situ hybridization also confirmed the presence of axl mRNA in thyroid carcinoma tissues. These findings suggest that Axl and Gas6 expression might be involved in childhood thyroid tumorigenesis around Chernobyl.