• 第三軍醫(yī)大學(xué)西南醫(yī)院普外科（重慶400038）;

目的 探討RET原癌基因與分化性甲狀腺癌關(guān)系的研究進(jìn)展。
方法 采用文獻(xiàn)回顧的方法，對RET基因及編碼產(chǎn)物的結(jié)構(gòu)，參與的細(xì)胞內(nèi)信號轉(zhuǎn)導(dǎo)，以及RET基因與分化性甲狀腺癌的關(guān)系的研究進(jìn)展加以綜述。
結(jié)果 RET基因編碼酪氨酸激酶受體，參與細(xì)胞內(nèi)信號轉(zhuǎn)導(dǎo)，RET原癌基因重排是乳頭狀甲狀腺癌中常見的遺傳學(xué)事件。
結(jié)論 RET基因與分化性甲狀腺癌的發(fā)生、發(fā)展密切相關(guān)，是該類腫瘤治療的一個(gè)新靶點(diǎn)。

引用本文： 唐波,姜軍. RET原癌基因與分化性甲狀腺癌關(guān)系的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2004, 11(1): 89-91. doi: 復(fù)制

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1. Takahashi M， Ritz J， Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement [J]. Cell, 1985; 42(2)∶581.
2. Pasini B, Hofstra RM, Yin L,et al.The physical map of the human RET protooncogene [J]. Oncogene, 1995; 11(9)∶1737.
3. Durbec P, MarcosGutierrez CV, Kilkenny, et al.GDNF signalling through the Ret receptor tyrosine kinase [J]. Nature, 1996; 381(6585)∶789.
4. Besset V, Scott RP, Ibanez CF.Signaling complexes and proteinprotein interactions involved in the activation of the Ras and phosphatidylinositol 3kinase pathways by the cRet receptor tyrosine kinase [J]. J Biol Chem, 2000; 275(50)∶39159.
5. De Vita G, Melillo RM, Carlomagno F, et al. Tyrosine 1062 RETMEN2A mediates activation of Akt (protein kinase B) and mitogenactivated protein kinase pathways leading to PC12 cell survival [J]. Cancer Res, 2000; 60(14)∶3727.
6. Hayashi H, Ichihara M, Iwashita T, et al. Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell linederived neurotrophic factor [J]. Oncogene, 2000; 19(39)∶4469.
7. Alberti L, Borrello MG, Ghizzoni S, et al.Grb2 binding to the different isoforms of Ret tyrosine kinase [J]. Oncogene, 1998; 17(9)∶1079.
8. Arighi E, Alberti L, Torriti F, et al. Identification of Shc docking site on Ret tyrosine kinase [J]. Oncogene, 1997; 14(7)∶773.
9. Mercalli E, Ghizzoni S, Arighi E, et al.Key role of shc signaling in the transforming pathway triggered by Ret/ptc2 oncoprotein [J]. Oncogene, 2001; 20(27)∶3475.
10. Musholt TJ, Musholt PB, Khaladj N, et al.Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma [J]. Surgery, 2000; 128(6)∶984.
11. Roque L, Nunes VM, Ribeiro C, et al.Karyotypic charaterization of papillary thyroid carcinoma [J]. Cancer, 2001; 92(10)∶2529.
12. Rabes HM.Gene rearrangements in radiationinduced thyroid carcinogenesis [J]. Med Pediatr Oncol, 2001; 36(5)∶574.
13. Sheils OM, O’leary JJ, Sweeney EC, et al.Assessment of ret/PTC1 rearrange ments in neoplastic thyroid tissue using TaqMan RTPCR [J]. J Pathol， 2000; 192(1)∶32.
14. Mai KT, Vaccani JP, Thomas J, et al. Immunostaining for ret oncogene proteins in papillary thyroid carcinoma: a correlation of ret immunoreactivity and potential of lymph node metastasis [J]. Thyroid, 2001; 11(9)∶859.
15. Basolo F, Molinaro E, Agate L， et al.RET protein expression has no prognostic impact on the longterm outcome of papillary thyroid carcinoma [J]. Eur J Endocrinol, 2001; 145(5)∶599.
16. Salvatore G, Nagata S, Billaud M, et al. Generation and characterization of novel monoclonal antibodies to the Ret receptor tyrosine kinase [J]. Biochem Biophys Res Commun, 2002； 294(4)∶813.
17. Hennige AM, Lammers R, Hoppner W, et al.Inhibition of Ret oncogene activity by the protein tyrosine phosphatase SHP1 [J]. Endocrinology, 2001; 142(10)∶4441.
18. Carlomagno F, Vitagliano D, Guida T, et al.The kinase inhibitor PP1 blocks tumor igenesis induced by RET oncogenes [J].Cancer Res, 2002; 62(4)∶1077.
  1. 1. Takahashi M， Ritz J， Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement [J]. Cell, 1985; 42(2)∶581.
  2. 2. Pasini B, Hofstra RM, Yin L,et al.The physical map of the human RET protooncogene [J]. Oncogene, 1995; 11(9)∶1737.
  3. 3. Durbec P, MarcosGutierrez CV, Kilkenny, et al.GDNF signalling through the Ret receptor tyrosine kinase [J]. Nature, 1996; 381(6585)∶789.
  4. 4. Besset V, Scott RP, Ibanez CF.Signaling complexes and proteinprotein interactions involved in the activation of the Ras and phosphatidylinositol 3kinase pathways by the cRet receptor tyrosine kinase [J]. J Biol Chem, 2000; 275(50)∶39159.
  5. 5. De Vita G, Melillo RM, Carlomagno F, et al. Tyrosine 1062 RETMEN2A mediates activation of Akt (protein kinase B) and mitogenactivated protein kinase pathways leading to PC12 cell survival [J]. Cancer Res, 2000; 60(14)∶3727.
  6. 6. Hayashi H, Ichihara M, Iwashita T, et al. Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell linederived neurotrophic factor [J]. Oncogene, 2000; 19(39)∶4469.
  7. 7. Alberti L, Borrello MG, Ghizzoni S, et al.Grb2 binding to the different isoforms of Ret tyrosine kinase [J]. Oncogene, 1998; 17(9)∶1079.
  8. 8. Arighi E, Alberti L, Torriti F, et al. Identification of Shc docking site on Ret tyrosine kinase [J]. Oncogene, 1997; 14(7)∶773.
  9. 9. Mercalli E, Ghizzoni S, Arighi E, et al.Key role of shc signaling in the transforming pathway triggered by Ret/ptc2 oncoprotein [J]. Oncogene, 2001; 20(27)∶3475.
  10. 10. Musholt TJ, Musholt PB, Khaladj N, et al.Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma [J]. Surgery, 2000; 128(6)∶984.
  11. 11. Roque L, Nunes VM, Ribeiro C, et al.Karyotypic charaterization of papillary thyroid carcinoma [J]. Cancer, 2001; 92(10)∶2529.
  12. 12. Rabes HM.Gene rearrangements in radiationinduced thyroid carcinogenesis [J]. Med Pediatr Oncol, 2001; 36(5)∶574.
  13. 13. Sheils OM, O’leary JJ, Sweeney EC, et al.Assessment of ret/PTC1 rearrange ments in neoplastic thyroid tissue using TaqMan RTPCR [J]. J Pathol， 2000; 192(1)∶32.
  14. 14. Mai KT, Vaccani JP, Thomas J, et al. Immunostaining for ret oncogene proteins in papillary thyroid carcinoma: a correlation of ret immunoreactivity and potential of lymph node metastasis [J]. Thyroid, 2001; 11(9)∶859.
  15. 15. Basolo F, Molinaro E, Agate L， et al.RET protein expression has no prognostic impact on the longterm outcome of papillary thyroid carcinoma [J]. Eur J Endocrinol, 2001; 145(5)∶599.
  16. 16. Salvatore G, Nagata S, Billaud M, et al. Generation and characterization of novel monoclonal antibodies to the Ret receptor tyrosine kinase [J]. Biochem Biophys Res Commun, 2002； 294(4)∶813.
  17. 17. Hennige AM, Lammers R, Hoppner W, et al.Inhibition of Ret oncogene activity by the protein tyrosine phosphatase SHP1 [J]. Endocrinology, 2001; 142(10)∶4441.
  18. 18. Carlomagno F, Vitagliano D, Guida T, et al.The kinase inhibitor PP1 blocks tumor igenesis induced by RET oncogenes [J].Cancer Res, 2002; 62(4)∶1077.