RET receptor expression in thyroid follicular epithelial cell-derived tumors

The RET proto-oncogene encodes a receptor tyrosine kinase for transforming growth factor-beta-related neurotrophic factors, which include GDNF and neu rturin, The expression of RET proto-oncogene was detected in several tissue s, such as spleen, thymus, lymph nodes, salivary gland, and spinal cord, an d in several neural crest-derived cell lines. RET expression in the thyroid gland was reported to be restricted to neural crest-derived C cells. The p resence of RET mRNA or protein has not yet been reported in thyroid follicu lar cells. We previously demonstrated the expression of oncogenic rearrange d versions of RET in papillary thyroid carcinomas: tumors derived from thyr oid follicular cells. To assess the expression of the normal RET proto-onco gene in follicular cells, we analyzed its expression in a panel of neoplasi as originating from thyroid follicular epithelial cells: papillary carcinom as and both follicular adenomas and carcinomas. We also demonstrated the pr esence of RET normal transcripts in two follicular thyroid carcinoma lymph node metastases, Moreover, we found the presence of the RET/ELE1 transcript , the reciprocal complementary form of the oncogenic fusion transcript ELE1 /RET, in a papillary thyroid carcinoma specimen expressing the RET/PTC3 onc ogene, thus demonstrating that the RET promoter is active in those cells af ter rearrangement. Finally, we show that in a papillary carcinoma-derived c ell line expressing the proto-RET receptor and the related GFR alpha 2 co-r eceptor, GDNF treatment induced RET tyrosine phosphorylation and subsequent signal transduction pathway, indicating that RET could be active in thyroi d follicular cells.