Characterization of ret oncogenic activation in MEN2 inherited cancer syndromes

Endocrinology
S XingS M Jhiang

Abstract

Germline mutations of c-ret, encoding a receptor-type tyrosine kinase, were found to be associated with variants of multiple endocrine neoplasia type 2 (MEN2A, MEN2B), and familial medullary thyroid carcinoma. NIH/3T3 stable transfectants expressing RET with a mutation of MEN2A (MEN2A/RET) or MEN2B (MEN2B/RET) gained a transformed morphology, formed colonies in soft agar, and formed tumors in nude mice. These results confirmed that both MEN2A/RET and MEN2B/RET exert dominant transforming activities in NIH/3T3 cells. However, in contrast to their clinical manifestation, transfectants expressing MEN2A/RET exhibited a higher tumorigenicity in nude mice than transfectants expressing MEN2B/RET may depend on the presence of its ligand and/or substrates that are absent in NIH/3T3 cells. No change in the cellular localization of the mutated RET proteins was observed compared to c-RET. Interestingly, ret activation in NIT/3T3 cells appeared to be associated with up-regulation of homologous gap-junctional intercellular communication and increased expression of a gap-junctional protein, connexin43.

Citations

Nov 10, 2000·Journal of Medical Genetics·J R Hansford, L M Mulligan
Apr 21, 1999·The Journal of Pathology·D Locke
Aug 31, 2019·Environmental and Molecular Mutagenesis·Kelly L HarrisBarbara L Parsons
Dec 15, 2000·Oncogene·S M Jhiang
Apr 22, 2006·Arquivos brasileiros de endocrinologia e metabologia·Marcelo A C G dos SantosSergio P de Almeida Toledo
Mar 28, 1998·The Journal of Biological Chemistry·S XingS M Jhiang
Apr 4, 1997·The Journal of Biological Chemistry·Q TongS M Jhiang
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·A O HoffR F Gagel

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