Molecular studies on the regulation of parathyroid cell growth and the mechanisms of parathyroid adenoma development

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We have attempted systematical expression cloning of oncogenes from a cDNA library derived from a parathyroid adenoma, and functional analysis of these genes. An isoform of keratinocyte growth factor receptor, which has an alternatively spliced form of C-terminus, was isolated, and found to be expressed in parathyroid adenoma, but not in parathyroid cancer or hyperplasia. Two possibilities, the variant C terminus having functions of activating the signal transduction or the wild-type C terminus carrying the functions of inhibiting the signaling. To clarify these possibilities, we used the Yeast Two Hybrid system to clone the molecules that can bind to these C terminus portion of the keratinocyte growth factor receptor, which leads to the discovery of several molecules. We are now in the middle of characterizing the function of these clones.