Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer.
Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer.
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DOI：
10.1038/s41598-021-94711-6
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发表时间：
2021-07-28
影响因子：
4.6
通讯作者：
Kugoh H
中科院分区：
文献类型：
--
作者：
Yagyu T;Ohira T;Shimizu R;Morimoto M;Murakami Y;Hanaki T;Kihara K;Matsunaga T;Yamamoto M;Tokuyasu N;Sakamoto T;Fujiwara Y;Kugoh H
在胰腺癌组织中发现3号染色体短臂（3p）区域存在频繁的杂合性丢失（洛），提示该区域可能存在抑癌基因。然而，该区域的洛缺失在PC发生发展中的功能意义尚未明确。人端粒酶逆转录酶基因（human telomerase reverse transcriptase gene，hTERT）是恶性肿瘤增殖和致瘤的重要基因。我们以前证明，hTERT的表达被抑制的人3号染色体在几个癌细胞系的介绍。为了研究PC中3号染色体上假定的TERT抑制基因的功能作用，我们使用微细胞介导的染色体转移将完整的人3号染色体引入人PK9和小鼠LTPA PC细胞系中。PK9微细胞杂交与引入的人3号染色体表现出显着的形态变化和快速生长停滞。有趣的是，与含有人4号染色体的LTPA#4细胞和亲本LTPA细胞相比，具有引入的人3号染色体的LTPA细胞（LTPA#3）的微细胞杂交克隆显示出mTert转录、细胞增殖和侵袭的抑制。此外，mTert的启动子活性在LTPA#3中下调。此外，我们通过在任意区域转移截短的染色体，证实了3p21.3区域中存在TERT调节基因。这些结果提供了重要信息的功能意义的洛在3 p的PC的发展和进展。
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.
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影响因子：
5.2
作者：
Kugoh H;Ohira T;Oshimura M
通讯作者：
Oshimura M
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50.5
作者：
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影响因子：
7.8
作者：
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Wright WE