Letter re: Id1 Gene Expression in Hyperplastic and Neoplastic Thyroid Tissues

Rao, Annavarapu Srinivas; Goretzki, P. E.; Köhrle, Josef; Brabant, Georg

doi:10.1210/jc.2005-0952

Cited by 9 publications

(5 citation statements)

References 10 publications

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“…Next, we characterized three human FTC cell lines, FTC‐133, FTC‐238, and WRO (Figure and Supporting Information Figure S3). FTC‐133 and FTC‐238 originate from the same patient at different time points and disease stages, where FTC‐133 is a local lymph node metastasis and FTC‐238 is a late distant hematogenous metastasis. WRO is derived from a metastasis from another FTC patient and is the only DTC cell line analyzed here that does not harbor an activating TERT promoter mutation.…”

Section: Resultsmentioning

confidence: 99%

Characterization of human telomerase reverse transcriptase promoter methylation and transcription factor binding in differentiated thyroid cancer cell lines

Avin

Wang

Gilpatrick

et al. 2019

Genes Chromosomes & Cancer

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Telomerase reverse transcriptase (TERT) activation plays an important role in cancer development by enabling the immortalization of cells. TERT regulation is multifaceted, and its promoter methylation has been implicated in controlling expression through alteration in transcription factor binding. We have characterized TERT promoter methylation, transcription factor binding, and TERT expression levels in five differentiated thyroid cancer (DTC) cell lines and six normal thyroid tissue samples by targeted bisulfite sequencing, ChIP‐qPCR, and qRT‐PCR. DTC cell lines express varying levels of TERT and exhibit TERT promoter methylation patterns similar to patterns seen in other telomerase positive cancer cell lines. The minimal promoter immediately surrounding the transcription start site is hypomethylated, while further upstream portions show dense methylation. In contrast, the TERT promoter in normal thyroid tissue is largely unmethylated throughout and expresses TERT minimally. Transcription factor binding is also affected by TERT mutation status. The E‐twenty‐six (ETS) factor GABPA exhibits TERT binding in the TERT mutant DTC cells only, and allele‐specific methylation patterns at the minimal promoter were observed as well, which may indicate allele‐specific factor recruitment at the minimal promoter. Furthermore, we identified binding sites for activators MYC and GSC in the hypermethylated upstream region, pointing to its possible importance in TERT regulation. Overall, TERT expression and telomerase activity depend on the interplay of multiple regulatory mechanisms including TERT promoter methylation, mutation status, and recruitment of transcription factors. This work explores of the interplay between these regulatory mechanisms and offers insight into cellular control of active telomerase in human cancer.

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Section: Resultsmentioning

confidence: 99%

Characterization of human telomerase reverse transcriptase promoter methylation and transcription factor binding in differentiated thyroid cancer cell lines

Avin

Wang

Gilpatrick

et al. 2019

Genes Chromosomes & Cancer

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“…Cell lines, culture conditions, and TERT mutation status Papillary [TPC-1 (30), BCPAP (31)] and follicular thyroid cancer cell lines [FTC-133 (32), FTC-238 (32), and WRO (33)] were kindly provided by Dr. Motoyasu Saji (The Ohio State University Wexner Medical Center, Columbus, OH). Cell lines were grown as previously described (7).…”

Section: Methodsmentioning

confidence: 99%

Characterization of Allele-Specific Regulation of Telomerase Reverse Transcriptase in Promoter Mutant Thyroid Cancer Cell Lines

McKelvey

Gilpatrick

Wang

et al. 2020

Thyroid

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Background: Telomerase reverse transcriptase (TERT) promoter mutations play a role in carcinogenesis and are found in both tumors and cancer cell lines. TERT promoter methylation, transcription factor binding, chromatin remodeling, and alternative splicing are also known to play an integral role in TERT regulation. Methods: Using nanopore Cas9 targeted sequencing, we characterized allele-specific methylation in thyroid cancer cell lines heterozygous for the TERT promoter mutation. Furthermore, using chromatin immunoprecipitation followed by Sanger sequencing, we probed allele-specific binding of the transcription factors GABPA (GA binding protein transcription factor subunit alpha) and MYC, as well as the chromatin marks H3K4me3 and H3K27me3. Finally, using coding single nucleotide polymorphisms and the long-read sequencing, we examined complementary DNA for monoallelic expression (MAE). Results: We found the mutant TERT promoter allele to be significantly less methylated than wild type, while more methylated in the gene body in heterozygous TERT mutant cell lines. We demonstrated that the transcriptional activators GABPA and MYC bind only to the mutant TERT allele. In addition, the activating and repressive chromatin marks H3K4me3 and H3K27me3, respectively, bind mutant and wild-type alleles exclusively. Finally, in heterozygous mutant cell lines, TERT exhibits MAE from the mutant allele only. Conclusions: In summary, by employing new long-read sequencing methods, we were able to definitively demonstrate allele-specific DNA methylation, histone modifications, transcription factor binding, and the resulting monoallelic transcription in cell lines with heterozygous TERT mutations.

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“…No mouse thyroid cancerderived cell lines were available. The three human FTC lines were derived from the same patient; the higher the number, the more distant the metastasis was, which can be considered less differentiated (65). The expression levels of STC1 mRNA increased as the number became larger in FTC lines of cells, while STC1 expression was lower in RO82-W-1…”

Section: Effect Of Partial Thyroidectomy On Thyroid Sp Cells and Theimentioning

confidence: 99%

Expression of Stanniocalcin 1 in Thyroid Side Population Cells and Thyroid Cancer Cells

Hayase

Sasaki

Matsubara

et al. 2015

Thyroid

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Letter re: Id1 Gene Expression in Hyperplastic and Neoplastic Thyroid Tissues

Cited by 9 publications

References 10 publications

Characterization of human telomerase reverse transcriptase promoter methylation and transcription factor binding in differentiated thyroid cancer cell lines

Characterization of human telomerase reverse transcriptase promoter methylation and transcription factor binding in differentiated thyroid cancer cell lines

Characterization of Allele-Specific Regulation of Telomerase Reverse Transcriptase in Promoter Mutant Thyroid Cancer Cell Lines

Expression of Stanniocalcin 1 in Thyroid Side Population Cells and Thyroid Cancer Cells

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