Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer

Abstract Frequent loss of heterozygosity (LOH) on the short arm of human chromosome 3 (3p) region has been found in pancreatic cancer (PC), which suggests the likely presence of tumor suppressor genes in this region. However, the functional significance of LOH in this region in the development of PC...

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Autores principales:	Takuki Yagyu, Takahito Ohira, Ryutaro Shimizu, Masaki Morimoto, Yuki Murakami, Takehiko Hanaki, Kyoichi Kihara, Tomoyuki Matsunaga, Manabu Yamamoto, Naruo Tokuyasu, Teruhisa Sakamoto, Yoshiyuki Fujiwara, Hiroyuki Kugoh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9769e5090884b229262119c848de894
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spelling	oai:doaj.org-article:d9769e5090884b229262119c848de8942021-12-02T16:06:43ZHuman chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer10.1038/s41598-021-94711-62045-2322https://doaj.org/article/d9769e5090884b229262119c848de8942021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94711-6https://doaj.org/toc/2045-2322Abstract Frequent loss of heterozygosity (LOH) on the short arm of human chromosome 3 (3p) region has been found in pancreatic cancer (PC), which suggests the likely presence of tumor suppressor genes in this region. However, the functional significance of LOH in this region in the development of PC has not been clearly defined. The human telomerase reverse transcriptase gene (hTERT) contributes to unlimited proliferative and tumorigenicity of malignant tumors. We previously demonstrated that hTERT expression was suppressed by the introduction of human chromosome 3 in several cancer cell lines. To examine the functional role of putative TERT suppressor genes on chromosome 3 in PC, we introduced an intact human chromosome 3 into the human PK9 and murine LTPA PC cell lines using microcell-mediated chromosome transfer. PK9 microcell hybrids with an introduced human chromosome 3 showed significant morphological changes and rapid growth arrest. Intriguingly, microcell hybrid clones of LTPA cells with an introduced human chromosome 3 (LTPA#3) showed suppression of mTert transcription, cell proliferation, and invasion compared with LTPA#4 cells containing human chromosome 4 and parental LTPA cells. Additionally, the promoter activity of mTert was downregulated in LTPA#3. Furthermore, we confirmed that TERT regulatory gene(s) are present in the 3p21.3 region by transfer of truncated chromosomes at arbitrary regions. These results provide important information on the functional significance of the LOH at 3p for development and progression of PC.Takuki YagyuTakahito OhiraRyutaro ShimizuMasaki MorimotoYuki MurakamiTakehiko HanakiKyoichi KiharaTomoyuki MatsunagaManabu YamamotoNaruo TokuyasuTeruhisa SakamotoYoshiyuki FujiwaraHiroyuki KugohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuki Yagyu Takahito Ohira Ryutaro Shimizu Masaki Morimoto Yuki Murakami Takehiko Hanaki Kyoichi Kihara Tomoyuki Matsunaga Manabu Yamamoto Naruo Tokuyasu Teruhisa Sakamoto Yoshiyuki Fujiwara Hiroyuki Kugoh Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
description	Abstract Frequent loss of heterozygosity (LOH) on the short arm of human chromosome 3 (3p) region has been found in pancreatic cancer (PC), which suggests the likely presence of tumor suppressor genes in this region. However, the functional significance of LOH in this region in the development of PC has not been clearly defined. The human telomerase reverse transcriptase gene (hTERT) contributes to unlimited proliferative and tumorigenicity of malignant tumors. We previously demonstrated that hTERT expression was suppressed by the introduction of human chromosome 3 in several cancer cell lines. To examine the functional role of putative TERT suppressor genes on chromosome 3 in PC, we introduced an intact human chromosome 3 into the human PK9 and murine LTPA PC cell lines using microcell-mediated chromosome transfer. PK9 microcell hybrids with an introduced human chromosome 3 showed significant morphological changes and rapid growth arrest. Intriguingly, microcell hybrid clones of LTPA cells with an introduced human chromosome 3 (LTPA#3) showed suppression of mTert transcription, cell proliferation, and invasion compared with LTPA#4 cells containing human chromosome 4 and parental LTPA cells. Additionally, the promoter activity of mTert was downregulated in LTPA#3. Furthermore, we confirmed that TERT regulatory gene(s) are present in the 3p21.3 region by transfer of truncated chromosomes at arbitrary regions. These results provide important information on the functional significance of the LOH at 3p for development and progression of PC.
format	article
author	Takuki Yagyu Takahito Ohira Ryutaro Shimizu Masaki Morimoto Yuki Murakami Takehiko Hanaki Kyoichi Kihara Tomoyuki Matsunaga Manabu Yamamoto Naruo Tokuyasu Teruhisa Sakamoto Yoshiyuki Fujiwara Hiroyuki Kugoh
author_facet	Takuki Yagyu Takahito Ohira Ryutaro Shimizu Masaki Morimoto Yuki Murakami Takehiko Hanaki Kyoichi Kihara Tomoyuki Matsunaga Manabu Yamamoto Naruo Tokuyasu Teruhisa Sakamoto Yoshiyuki Fujiwara Hiroyuki Kugoh
author_sort	Takuki Yagyu
title	Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
title_short	Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
title_full	Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
title_fullStr	Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
title_full_unstemmed	Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer
title_sort	human chromosome 3p21.3 carries tert transcriptional regulators in pancreatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9769e5090884b229262119c848de894
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_version_	1718384935271661568

Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer

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