日本研究人員日前宣布,，他們發(fā)現(xiàn)了能夠遏制癌細(xì)胞增殖時必需的端粒酶發(fā)揮作用的基因,。這一成果有助開發(fā)新的癌癥診療方法。
端粒位于染色體末端,，正常的細(xì)胞每分裂一次,，端粒就會變短一次，細(xì)胞從而老化并最終死亡,。然而在癌細(xì)胞中,，端粒酶會防止端粒變短，導(dǎo)致癌細(xì)胞不斷增殖,。
日本鳥取大學(xué)副教授久鄉(xiāng)裕之領(lǐng)導(dǎo)的研究小組,，把人的染色體逐個移植到實(shí)驗(yàn)鼠的癌細(xì)胞中進(jìn)行培養(yǎng)，發(fā)現(xiàn)在移植了第5號染色體的癌細(xì)胞中,，端粒酶的功能會受到遏制,。研究進(jìn)一步發(fā)現(xiàn)，遏制端粒酶發(fā)揮作用的是第5號染色體中的PITX1基因,。研究人員將這種基因移植到實(shí)驗(yàn)鼠的癌細(xì)胞中,，其端粒酶功能也受到遏制，使得癌細(xì)胞無法增殖,。
這一成果已刊登在美國科學(xué)雜志《分子與細(xì)胞生物學(xué)》網(wǎng)絡(luò)版上,。（生物谷Bioon.com）
生物谷推薦原文出處：
Mol. Cell. Biol. doi:10.1128/MCB.00470-10
Identification of PITX1 as a TERT suppressor gene located on human chromosome 5
Dong-Lai Qi, Takahito Ohhira, Chikako Fujisaki, Toshiaki Inoue, Tsutomu Ohta, Mitsuhiko Osaki, Eriko Ohshiro, Tomomi Seko, Shinsuke Aoki, Mitsuo Oshimura, and Hiroyuki Kugoh*
Abstract
Telomerase, a ribonucleoprotein enzyme that maintains telomere length, is crucial for cellular immortalization and cancer progression. Telomerase activity is primarily attributed to the expression of telomerase reverse transcriptase (TERT). Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose expression leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity.
