Molecular biology of the MEN2 gene.
Cancer is a genetic disease caused by 'gain of function' mutations of oncogenes and 'loss of function' mutations of tumour suppressors and of genes involved in DNA repair mechanisms. The RET gene encodes a tyrosine kinase receptor for molecules belonging to the glial cell line-derived neurotrophic factor (GDNF) family. RET is a paradigmatic example of how different mutations of a single gene can lead to different neoplastic phenotypes. Indeed, gene rearrangements, often caused by chromosomal inversions, activate the oncogenic potential of RET in a fraction of human thyroid papillary carcinomas. On the other hand, different point mutations activate RET in familial multiple endocrine neoplasia syndromes familial medullary thyroid carcinoma (FMTC), MEN-2A and MEN-2B. Little information is so far available on the biochemical mechanisms by which the potent transforming and mitogenic signals of RET are delivered to the nucleus. However, recent data indicate coupling to the Shc-Ras-MAPK pathway as a necessary step in RET signal transduction.
Centro di Endocrinologia ed Oncologia Sperimentale del CNR/Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli, Naples, Italy.
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D002291:Carcinoma, Papillary / Q000235:genetics; D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000235:genetics
D029721:Drosophila Proteins; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila