Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes
A variant located on 14q13.3 nearest to thyroid transcription factor-1 (TTF1) predisposes individuals to thyroid cancer, but whether this variant is related to the RET/PTC rearrangement associated with human papillary thyroid carcinomas (PTCs) is unknown. The aims of this study were to investigate t...
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| Format: | Online |
| Language: | English |
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Society for Endocrinology
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796879/ |
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pubmed-3796879 |
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pubmed-37968792013-12-01 Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes Endo, Toyoshi Kobayashi, Tetsuro Research A variant located on 14q13.3 nearest to thyroid transcription factor-1 (TTF1) predisposes individuals to thyroid cancer, but whether this variant is related to the RET/PTC rearrangement associated with human papillary thyroid carcinomas (PTCs) is unknown. The aims of this study were to investigate the effects of RET/PTC1 on the expression of thyroid-specific genes in thyrocytes and their relationship with malignant transformation of the thyrocytes. In the absence or presence of TSH, an extracellular signal-regulated kinase was phosphorylated in FRTL5 cells that stably expressed RET/PTC1, and these cells grew independently of TSH. FRTL (RET/PTC1) cells produced 566% more thyroglobulin mRNA and 474% more Na+/I− symporter mRNA than did the control FRTL (pcDNA) cells. FRTL (RET/PTC1) cells expressed 468% more Ttf1 mRNA than did FRTL (pcDNA) cells, but these two cell types did not differ significantly with respect to Pax8 or Ttf2 mRNA levels. When FRTL (RET/PTC1) cells and FRTL (pcDNA), cells were injected into each of nine nude mice, each mouse developed a single tumor at the site of FRTL (RET/PTC1) cell injection; in contrast, tumor formation never occurred at sites of FRTL (cDNA) cells injection. Tumors resulting from FRTL (RET/PTC1) cells retained 125I-uptake activity; moreover, the cells invaded into surrounding skeletal muscle. When overexpression of Ttf1 in FRTL (RET/PTC1) cells was silenced, the cells completely lost their tumorigenic potential. Exogenous TTF1 cDNA enhanced the tumorigenicity of BHP18-21v cells, human PTC cells that express RET/PTC1, in nude mice. These results indicated that concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to FRTL5 and BHP18-21v cells in nude mice. Society for Endocrinology 2013-12 /pmc/articles/PMC3796879/ /pubmed/24014739 http://dx.doi.org/10.1530/ERC-13-0310 Text en © 2013 Society for Endocrinology http://creativecommons.org/licenses/by/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/deed.en_GB) |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Endo, Toyoshi Kobayashi, Tetsuro |
| spellingShingle |
Endo, Toyoshi Kobayashi, Tetsuro Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| author_facet |
Endo, Toyoshi Kobayashi, Tetsuro |
| author_sort |
Endo, Toyoshi |
| title |
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| title_short |
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| title_full |
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| title_fullStr |
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| title_full_unstemmed |
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes |
| title_sort |
concurrent overexpression of ret/ptc1 and ttf1 confers tumorigenicity to thyrocytes |
| description |
A variant located on 14q13.3 nearest to thyroid transcription factor-1 (TTF1) predisposes individuals to thyroid cancer, but whether this variant is related to the RET/PTC rearrangement associated with human papillary thyroid carcinomas (PTCs) is unknown. The aims of this study were to investigate the effects of RET/PTC1 on the expression of thyroid-specific genes in thyrocytes and their relationship with malignant transformation of the thyrocytes. In the absence or presence of TSH, an extracellular signal-regulated kinase was phosphorylated in FRTL5 cells that stably expressed RET/PTC1, and these cells grew independently of TSH. FRTL (RET/PTC1) cells produced 566% more thyroglobulin mRNA and 474% more Na+/I− symporter mRNA than did the control FRTL (pcDNA) cells. FRTL (RET/PTC1) cells expressed 468% more Ttf1 mRNA than did FRTL (pcDNA) cells, but these two cell types did not differ significantly with respect to Pax8 or Ttf2 mRNA levels. When FRTL (RET/PTC1) cells and FRTL (pcDNA), cells were injected into each of nine nude mice, each mouse developed a single tumor at the site of FRTL (RET/PTC1) cell injection; in contrast, tumor formation never occurred at sites of FRTL (cDNA) cells injection. Tumors resulting from FRTL (RET/PTC1) cells retained 125I-uptake activity; moreover, the cells invaded into surrounding skeletal muscle. When overexpression of Ttf1 in FRTL (RET/PTC1) cells was silenced, the cells completely lost their tumorigenic potential. Exogenous TTF1 cDNA enhanced the tumorigenicity of BHP18-21v cells, human PTC cells that express RET/PTC1, in nude mice. These results indicated that concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to FRTL5 and BHP18-21v cells in nude mice. |
| publisher |
Society for Endocrinology |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796879/ |
| _version_ |
1612018324002045952 |