Miura N, Onuki N, Rathi A, Virmani A, Nakamoto S, Kishimoto Y, Murawaki Y, Kawasaki H, Hasegawa J, Oshimura M, Travis W D, Gazdar A F
Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
Br J Cancer. 2001 Nov 16;85(10):1510-4. doi: 10.1054/bjoc.2001.2121.
Somatic cells express genes that suppress telomerase activity and these genes may be inactivated in tumour cells. We postulated that cancer cells acquire immortality by activation of telomerase by the loss of such a gene. We have reported recently that a telomerase repressor gene may be located on 10p15.1 by deletion mapping using microcell-mediated chromosome transfer (MMCT), radiated microcell fusion (RMF), fluorescent in situ hybridization (FISH) and STS analysis. To independently confirm this result, we correlated expression of RNA component of telomerase (hTR) as a marker of telomerase expression by in situ hybridization with allelic loss in pulmonary carcinoid tumours. Unlike most malignant tumours, pulmonary carcinoids (which are low-grade malignant tumours) are heterogeneous for telomerase expression. Loss of 5 closely spaced polymorphic markers on 10p15.1, especially D10S1728, were highly correlated with hTR expression. In an additional experiment, 10p15.1 showed higher and more significant correlation than any region of 3p where it has been predicted as another chromosomal location of telomerase repressor with allelic loss of the region. Our findings strongly suggest that 10p15.1 harbours a gene involved in repression of telomerase RNA component in human somatic cells and each putative repressor (on 3p and 10p) may act independently.
体细胞表达抑制端粒酶活性的基因，而这些基因在肿瘤细胞中可能失活。我们推测癌细胞通过失去这样一个基因而激活端粒酶从而获得永生。我们最近报道，利用微细胞介导的染色体转移（MMCT）、辐射微细胞融合（RMF）、荧光原位杂交（FISH）和序列标签位点（STS）分析，通过缺失定位，端粒酶抑制基因可能位于10p15.1。为了独立证实这一结果，我们通过原位杂交将端粒酶RNA成分（hTR）的表达作为端粒酶表达的标志物，与肺类癌肿瘤中的等位基因缺失进行了相关性分析。与大多数恶性肿瘤不同，肺类癌（低级别恶性肿瘤）的端粒酶表达具有异质性。10p15.1上5个紧密相邻的多态性标志物的缺失，尤其是D10S1728，与hTR表达高度相关。在另一项实验中，10p15.1显示出比3p的任何区域更高且更显著的相关性，3p被预测为端粒酶抑制基因的另一个染色体定位区域，该区域存在等位基因缺失。我们的研究结果强烈表明，10p15.1含有一个参与抑制人类体细胞中端粒酶RNA成分的基因，每个假定的抑制基因（位于3p和10p上）可能独立发挥作用。
