Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RET proto-oncogene is often activated through somatic rearrangements in papillary thyroid carcinomas (PTCs). Three main rearranged forms of RET have been described: RET/PTC1 and RET/PTC3, which arise from a paracentric inversion and RET/PTC2, which originates from a 10 : 17 translocation. We previously developed a dual-color FISH test to detect these RET rearrangements in interphase nuclei of thyroid lesions. This approach allowed us to detect a novel translocation involving the RET region, which was not detectable by RT - PCR with specific primers for known rearrangements. A combination of RT - PCR and RACE analyses finally led to the identification of the fusion gene, which involves the 5' portion of PCM-1, a gene coding for a centrosomal protein with distinct cell cycle distribution, and the RET tyrosine kinase (TK) domain. FISH analysis confirmed the chromosomal localization of PCM-1 on chromosome 8p21-22, a region commonly deleted in several tumors. Immunohistochemistry, using an antibody specific for the C-terminal portion of PCM-1 showed that the protein level is drastically decreased and its subcellular localization is altered in thyroid tumor tissue with respect to normal thyroid. However, heterozygosity is retained for seven microsatellite markers in the 8p21-22 region, suggesting that the non-rearranged PCM-1 allele is not lost and that the translocation is balanced. Oncogene (2000) 19, 4236 - 4242
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PMID:RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma. 1098 May 97

The receptor tyrosine kinase RET, with a known role in embryonic development and in human pathologies, is alternatively spliced to yield at least two functional isoforms, which differ only in their carboxyl terminal. Enigma protein is a member of the PDZ-LIM family and is known to interact with the short isoform of RET/PTC2, a chimeric oncoprotein isolated from papillary thyroid carcinoma. Here, we show that Enigma also interacts in intact cells with the short isoform of RET-wt and of its pathologic mutants associated to MEN2 syndromes, RET-C634R and RET-M918T. In contrast, Enigma binds all the corresponding RET long isoforms very poorly and colocalizes with short but not long RET/PTC2 isoforms. The RET docking tyrosine for Enigma is the last but one before the divergence between the two isoforms and we demonstrated that short-isoform-specific amino acid residues +2 to +4 to this tyrosine are required for the interaction of RET/PTC2 with Enigma.
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PMID:Differential interaction of Enigma protein with the two RET isoforms. 1217 11

Somatic rearrangement of the tyrosine kinase receptor RET is restricted to papillary thyroid carcinoma (PTC). The prevalence of RET/PTC1, RET/PTC2, and RET/PTC3 has been found to vary between 0% and 20% in most series of sporadic (nonradiation-induced) PTCs analyzed by type-specific reverse transcription-polymerase chain reaction (RT-PCR) alone. However, high prevalence reported from Taiwan (6 out of 11, 55%) indicates RET rearrangement is an important genetic lesion underlying the development of PTC in Taiwan. Because the high prevalence of RET rearrangements in Chinese patients was particularly striking, we were prompted to reexamine chimeric transcripts of RET/PTC1, RET/PTC2, and RET/PTC3 using the same experimental designs in a larger number of cases in the same population. RT-PCR was performed to amplify fusion products of RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET from frozen tissue of 105 sporadic PTCs. RT-PCR was also performed with two different primer sets for RET/PTC1, RET/PTC2, and RET/PTC3 followed by Southern hybridization in the first 62 tumors. In our study, RET/PTC1, RET/PTC2, and RET/PTC3 oncogenes were found in only 7 of 105 (7%) sporadic PTCs. Of these tumors, 3 involved RET/PTC1 and 4 involved RET/PTC3. No RET/PTC2 rearrangements were observed. In the first 62 tumor samples, another two different primer sets for each rearrangement also gave concordant results. Furthermore, application of Southern hybridization in these 62 PTCs did not identify additional tumor harboring RET chimeric transcripts. We identified one tumor as having an ELKS-RET rearrangement (1 of 105, 1%). In conclusion, we detected RET rearrangements in 8 of 105 (8%) sporadic PTCs in Taiwan, a much lower prevalence than previously reported for this population but comparable to those reported in other nations using similar methodology. RET chimeric oncogenes only account for a small fraction of PTCs in Taiwan.
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PMID:Low prevalence of RET rearrangements (RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET) in sporadic papillary thyroid carcinomas in Taiwan Chinese. 1587 54

Among different genetic factors involved in the pathogenesis of the papillary thyroid carcinoma (PTC), rearrangements of RET protooncogene (RET/PTC), as well as rearrangements of NTRK1 protooncogene are best known. The resulting hybrid oncogenes are found in PTCs with variable frequency, depending on the examined population. The relationship between these chromosomal aberrations and clinical outcome of PTCs remains still controversial. The study aimed at estimating the frequency of rearrangements of RET and/or NTRK1 protooncogenes in PTC in the Polish population, and at evaluating the possible relationships between the presence of RET and/or NTRK1 oncogenes and such parameters, as patient's age, gender, histopathological variant of tumor and clinical staging. Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction (duplex RT-PCR) and OneStep RT-PCR, respectively, in tumor tissues obtained from 33 patients with PTC. Rearrangements of the RET protooncogene (RET/PTC1, RET/PTC2 and RET/PTC3) were detected in 7 out of 33 PTC (21%), and rearrangements of NTRK1 [Trk-T1 and Trk(TPM3)] were detected in 4 out of 33 examined samples (12%). In none of the examined cases, did the RET and NTRK1 rearrangements occur in the same sample. No correlations were found between RET/PTC or Trk oncogenic sequences and patient's age, gender, the histopathological variant of PTC and the assignment to particular stage in clinical staging systems (TNM Staging, the University of Chicago clinical class, and Ohio State University Staging). Our study is the first one in which the frequency of NTRK1 rearrangements in PTC was reported for the Polish population. On the other hand, the frequency of RET rearrangements in PTC, as found by us, was similar to the previously reported results for the Polish population. Our results do not confirm the relationship between the structural aberrations in question and the clinical outcome of PTC.
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PMID:Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish population. 1648 15

We report the identification of proteins induced in response to RET/PTC2, an oncogene implicated in thyroid cancers. Anti-phosphotyrosine antibody affinity resin was used to purify Tyr(P)-containing and interacting proteins from 293T and NIH3T3 cells which were transfected with kinase active or inactive RET/PTC and RETMEN2 oncogenes. Proteins were separated by one-dimensional SDS-PAGE, extracted by in-gel digestion, and identified by MALDI-TOF peptide mass fingerprinting. The expression and tyrosine phosphorylation of Sam68, a protein implicated in mRNA nucleocytoplasmic translocation and splicing, were further examined in RET-transfected cells and thyroid tumors. Of relevance, cells transfected with RETMEN2B examined for anti-phosphotyrosine bound proteins, showed other proteins implicated in splicing: DEAD-box p68 RNA helicase, SYNCRIP, and hnRNP K. Western blotting analysis suggested that these proteins are singularly tyrosine phosphorylated in RETMEN2B-transfected cells, and that they constitutively bind with Sam68. The study concludes that regulation of splicing factors is likely to be important in RET-mediated thyroid carcinogenesis.
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PMID:RET oncoproteins induce tyrosine phosphorylation changes of proteins involved in RNA metabolism. 1684 37

Rare breast neoplasms resembling the tall-cell variant of papillary thyroid carcinoma have been reported. In addition, papillary carcinoma of the breast occasionally displays nuclear features reminiscent of papillary thyroid carcinoma. In this study, we evaluated 33 intraductal/intracystic papillary carcinomas of the breast for the presence and extent of nuclear overlap, grooves, clearing, and inclusions, as well as features of the tall-cell or columnar-cell variants of papillary thyroid carcinoma. RET rearrangements were assessed in a subset of these cases. Paired probes localizing to the centromeric and telomeric ends of the RET gene on chromosome 10 were used for FISH using a break-apart approach. Single round and nested PCR was performed to detect RET/PTC1, RET/PTC2, RET/PTC3 and ELKS-RET fusion transcripts. Nuclear overlap, grooves, stratification, and clearing were identified in 24 (73%), 14 (42%), 11 (33%), and 9 (27%) cases respectively, whereas nuclear inclusions and 'tall-cell' features were each seen in only one (3%) and two (6%) cases, respectively. Four of 19 tested cases displayed split FISH signals in a low percentage of cells and were considered borderline for RET rearrangement. All 19 tested cases with amplifiable RNA were negative for the four RET fusion transcripts evaluated by RT-PCR. Although papillary carcinomas of breast often display one or more cytoarchitectural features of papillary thyroid carcinoma, there is no evidence that RET rearrangements are involved.
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PMID:Papillary carcinoma of the breast lacks evidence of RET rearrangements despite morphological similarities to papillary thyroid carcinoma. 1954 46


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