Characterization of ret oncogenic activation in MEN2 inherited cancer syndromes
| Autor: | M J Oglesbee, Ernest L. Mazzaferri, J E Trosko, Sissy M. Jhiang, Shunhua Xing, Patricia A. Smanik |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Cytoplasm
congenital hereditary and neonatal diseases and abnormalities endocrine system medicine.medical_specialty endocrine system diseases Oncogene RET Gene Expression Mice Nude Multiple Endocrine Neoplasia Type 2a Multiple endocrine neoplasia type 2 Multiple Endocrine Neoplasia Type 2b Biology Transfection medicine.disease_cause 3T3 cells Mice Endocrinology Germline mutation Proto-Oncogene Proteins Internal medicine medicine Animals Drosophila Proteins Humans Fluorescent Antibody Technique Indirect neoplasms Cellular localization Mutation Cell Membrane Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Cancer 3T3 Cells medicine.disease medicine.anatomical_structure Connexin 43 Tyrosine kinase |
| Zdroj: | Endocrinology. 137:1512-1519 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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