Santoro M, Melillo R M, Carlomagno F, Visconti R, De Vita G, Salvatore G, Lupoli G, Fusco A, Vecchio G
Centro di Endocrinologia ed Oncologia Sperimentale del CNR/Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli, Naples, Italy.
J Intern Med. 1998 Jun;243(6):505-8. doi: 10.1046/j.1365-2796.1998.00330.x.
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.
癌症是一种由癌基因的“功能获得性”突变以及肿瘤抑制基因和参与DNA修复机制的基因的“功能丧失性”突变引起的遗传性疾病。RET基因编码一种针对属于胶质细胞系衍生神经营养因子（GDNF）家族分子的酪氨酸激酶受体。RET是一个典型例子，说明单个基因的不同突变如何导致不同的肿瘤表型。事实上，基因重排通常由染色体倒位引起，在一部分人类甲状腺乳头状癌中激活RET的致癌潜力。另一方面，不同的点突变在家族性多发性内分泌肿瘤综合征家族性甲状腺髓样癌（FMTC）、MEN-2A和MEN-2B中激活RET。到目前为止，关于RET强大的转化和有丝分裂信号传递到细胞核的生化机制的信息很少。然而，最近的数据表明，与Shc-Ras-MAPK途径偶联是RET信号转导的必要步骤。
