日本研究人员日前宣布，他们发现了能够遏制癌细胞增殖时必需的端粒酶发挥作用的基因。这一成果有助开发新的癌症诊疗方法。
端粒位于染色体末端，正常的细胞每分裂一次，端粒就会变短一次，细胞从而老化并最终死亡。然而在癌细胞中，端粒酶会防止端粒变短，导致癌细胞不断增殖。
日本鸟取大学副教授久乡裕之领导的研究小组，把人的染色体逐个移植到实验鼠的癌细胞中进行培养，发现在移植了第5号染色体的癌细胞中，端粒酶的功能会受到遏制。研究进一步发现，遏制端粒酶发挥作用的是第5号染色体中的PITX1基因。研究人员将这种基因移植到实验鼠的癌细胞中，其端粒酶功能也受到遏制，使得癌细胞无法增殖。
这一成果已刊登在美国科学杂志《分子与细胞生物学》网络版上。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
