Rompaey L V, Potter M, Adams C, Grosveld G
Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee, TN 38105, USA.
Oncogene. 2000 Nov 2;19(46):5244-50. doi: 10.1038/sj.onc.1203899.
The Tel gene is a major target of translocations in leukemia and loss of heterozygosity is regularly observed for the non-translocated allele, thus supporting the notion that Tel is a tumor suppressor. Most tumor suppressors influence cellular proliferation, differentiation and cell death and thereby prevent oncogenic transformation and genetic instability. We found that overexpression of Tel retards proliferation of many cell types, primary cells and immortalized cells, by inducing a G1 arrest. Tel's block of cellular proliferation is rescued by high seeding densities. Furthermore, Tel suppressed Ras-mediated colony growth in soft agar and tumor formation in nude mice. The Pointed and DNA binding (DB) domains of Tel were required for all Tel-induced phenotypes.
Tel基因是白血病中易位的主要靶点，并且经常观察到非易位等位基因的杂合性缺失，从而支持了Tel是一种肿瘤抑制基因的观点。大多数肿瘤抑制基因影响细胞增殖、分化和细胞死亡，从而防止致癌转化和遗传不稳定。我们发现，Tel的过表达通过诱导G1期阻滞来延缓多种细胞类型、原代细胞和永生化细胞的增殖。高接种密度可挽救Tel对细胞增殖的阻滞作用。此外，Tel抑制了软琼脂中Ras介导的集落生长以及裸鼠中的肿瘤形成。Tel诱导的所有表型都需要Tel的Pointed和DNA结合（DB）结构域。
