Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures

Department of Medicine, Nippon Medical School, Tokyo, Japan.

Recent reports indicate that a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth plates. These results suggest that FGFR-3 may be the receptor transducing growth inhibitory signals. Using reverse transcription-PCR we examined seven papillary thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma, FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell line. High levels of FGFR-3 protein were identified in cells stably transfected with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of these cells was threefold higher than that of control cells. Growth rates of cells overexpressing FGFR-3 were similar to those of control cells. However, cells overexpressing FGFR-3 continued to grow beyond the density at which control cells stopped proliferating. These results suggest that FGFR-3 in thyroid carcinoma is not involved strongly in the cell proliferation mechanism but may contribute to the malignant extension of some of the carcinomas by modifying cell contact signaling.

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