IDENTIFICATION AND CHARACTERIZATION OF NOVEL GENES MODULATED IN THE THYROID OF DOGS TREATED WITH METHIMAZOLE AND PROPYLTHIOURACIL

Induction of cell proliferation by mitogen or growth factor stimulatio n leads to the specific stimulation or repression of a large number of genes. To better understand differentiated epithelial cell growth reg ulation, we have initiated a study to identify genes which are regulat ed by the thyrotropin-dependent mitogenic pathway in dog thyroid cells . A thyroid cDNA library was prepared from a methimazole and propylthi ouracil-treated dog and differentially screened with probes derived fr om control or stimulated thyroids. Among 19 clones isolated, 6 encode known proteins (inwardly rectifying potassium channel, nucleosome asse mbly protein, ribosomal protein L7, elongation factor 1 alpha, non-mus cle myosin light chain, and heat shock protein 90 beta). The 13 others correspond to proteins whose function is unknown, Among them, 5 corre spond to mRNAs whose expression was modulated by mitogenic stimulation of thyrocytes in primary culture, A preliminary characterization of t wo of these cDNAs is reported: clone 5, which might represent a novel, atypical protein kinase, and clone 3, which contains ankyrin-like rep eats, suggesting that it might interact with other proteins.