Disease relevance of PTC

• Moreover, the transcript coded for by the fused gene was detected in an additional PTC-positive human papillary carcinoma for which mRNA was available [1].
• To identify the mechanism leading to the generation of the oncogenic sequence RET/PTC, a combined cytogenetic and molecular analysis of several cases of papillary thyroid carcinomas was done [2].
• Thyroid epithelial cells frequently express one or more members of the rearranged during transfection/papillary thyroid carcinoma (RET/PTC) fusion oncogene family during early stages of cancer, and fusion gene transcripts have been found in inflammatory conditions of the thyroid such as the autoimmune disease, Hashimoto's thyroiditis [3].
• Detection of retTPC/PTC transcripts in thyroid adenomas and adenomatous goiter by an RT-PCR method [4].
• In Japanese patients, one of 11 papillary thyroid carcinomas, four of 19 follicular adenomas and one of two adenomatous goiters were positive for the transcript, indicating that the involvement of retTPC/PTC is not specific to papillary thyroid carcinomas [4].

Psychiatry related information on PTC

• Individual differences in taste perception have been explained in part by variations in peripheral innervation associated with the genetic ability to taste the bitter substances PTC and PROP [5].

High impact information on PTC

• A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region [6].
• We designated this transforming gene PTC (for papillary thyroid carcinoma) [1].
• PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas [1].
• The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression [7].
• No LOH was observed for loci mapped to chromosome 10 in PTC [8].

Chemical compound and disease context of PTC

• Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC) [8].
• Constitutive activation of the RET proto-oncogene in papillary thyroid carcinomas results from rearrangements linking the promoter(s) and N-terminal domains of unrelated genes to the C-terminus of RET tyrosine kinase (RET/PTC) [9].
• The aim of the present review is to analyse the available data supporting the role for the PTC in orchestrating renal interstitial fibrosis in diabetic nephropathy as a result of glucose-dependent alterations in PTC function [10].
• Lymph node metastases at presentation are common in PTC and MTC (about one third of patients at presentation), but are rare in other types of thyroid malignancy, though HCC frequently recurs in lymph nodes [11].

Biological context of PTC

• Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC [8].
• Three forms of the ret/PTC oncogene have been identified; the two most common forms, ret/PTC-1 and ret/PTC-3, both result from a paracentric inversion, of the long arm of chromosome 10 [12].
• Moreover, a subset of the PTC, PTR, and Hh-r proteins have the same RNAi phenotypes, indicating that they have the potential to participate in the same processes [13].
• PTC and anaplastic thyroid carcinomas did not show significant down-regulation, and thus, caveolin-1 may become a useful molecular marker to differentiate the various histologies of thyroid malignancies [14].
• Nuclear envelope irregularity is induced by RET/PTC during interphase [15].

Anatomical context of PTC

• PTC, a vertebrate homolog of this Drosophila gene, is genetically downstream of Sonic hedgehog (Shh) in the limb bud [16].
• We analyze PTC expression during chicken neural and somite development and find it expressed in all regions of these tissues known to be responsive to Sonic hedgehog signal [16].
• As in the limb bud, ectopic expression of Sonic hedgehog leads to ectopic induction of PTC in the neural tube and paraxial mesoderm [16].
• Primary cultures of human thyroid epithelial cells were infected with a RET/PTC retroviral construct [17].
• A signaling pathway downstream of RET/ PTC leads to restructuring of the nuclear envelope and chromatin, and the signal does not depend entirely, if at all, on a RAS pathway [17].

Associations of PTC with other chemical compounds

• Tyrosine 1062 is essential for RET/PTC-mediated activation of the Ras/ERK pathway [18].
• Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells [19].
• In cultured MC and PTC, aldosterone induced significant increases in CTGF gene expression and protein synthesis associated with increased collagen synthesis, which was abolished by prior treatment with spironolactone [20].
• To demonstrate the utility of the new methodology, the anti-diabetes drug (-)-ragaglitazar 24 was synthesized in six steps from a key 2-alkoxy-3-p-phenoxypropionic acid 26 that was made using PTC glycolate alkylation [21].
• The phenylthiocarbamide nontaster trait was linked to three single nucleotide polymorphisms occurring in the PTC gene [22].

Gene context of PTC

• By combining expression profiles with mutational status, we defined distinct expression profiles for the BRAF, RET/PTC and RAS mutation groups [23].
• Taken together, these results suggest that human thyroid cancers bearing RET/PTC rearrangements may use the CXCR4/SDF-1alpha receptor-ligand pathway to proliferate, survive and migrate [24].
• We found that RET/PTC expression phosphorylates the Y701 residue of STAT1, a type II interferon (IFN)-responsive protein [25].
• In this study, we show that RET/PTC associates with signal transducer and activator of transcription 3 (STAT3) and activates it by the specific phosphorylation of the tyrosine 705 residue [26].
• Upregulation of CD44 was dependent on RET/PTC Y1062, as well [19].

Analytical, diagnostic and therapeutic context of PTC

• Morphological scoring by two independent cytopathologists shows RET/PTC expression by immunohistochemistry to be highly associated (p << 0.0001) with an irregular nuclear contour and a euchromatic appearance compared with non-expressing cells in the same cultures [17].
• The altered nuclear morphology is not due to gene transfer or transformation per se as primary thyroid cell cultures infected with a retroviral H-RAS construct differ from RET/PTC-infected cells by showing round nuclear envelopes and coarser chromatin, as determined by the independent scoring of two cytopathologists (p << 0.0001) [17].
• In several independent RT-PCR experiments using different portions of the same positive carcinoma tissue, retTPC/PTC transcript was always detected [4].
• A standard treatment approach was developed which consisted of ERCP for diagnosis, preoperative PTC with the placement of stents, CT drainage immediately after the PTC for drainage of biliary ascites, and usually Roux-en-Y hepaticojejunostomy with placement of O-rings for future biliary access if necessary [27].
• Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation [26].

References