Thymidylate synthase as an oncogene: A novel role for an essential DNA synthesis enzyme

被引：170

作者：

Rahman, L

Voeller, D

Rahman, M

Lipkowitz, S

Allegra, C

Barrett, JC

Kaye, FJ

Zajac-Kaye, M ^{[1
]}

机构：

[1] NCI, NIH, Ctr Canc Res, Basic Res Lab, Bethesda, MD 20892 USA

[2] NCI, NIH, Ctr Canc Res, Mol Therapeut Program, Bethesda, MD 20892 USA

[3] NCI, NIH, Ctr Canc Res, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA

[4] NCI, NIH, Ctr Canc Res, Lab Biosyst & Canc, Bethesda, MD 20892 USA

[5] NCI, NIH, Ctr Canc Res, Dept Genet, Bethesda, MD 20892 USA

来源：

CANCER CELL | 2004年 / 5卷 / 04期

关键词：

D O I：

10.1016/S1535-6108(04)00080-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Thymidylate synthase (TS) is an E2F1-regulated enzyme that is essential for DNA synthesis and repair. TS protein and mRNA levels are elevated in many human cancers, and high TS levels have been correlated with poor prognosis in patients with colorectal, breast, cervical, bladder, kidney, and non-small cell lung cancers. In this study, we show that ectopic expression of catalytically active TS is sufficient to induce a transformed phenotype in mammalian cells as manifested by foci formation, anchorage independent growth, and tumor formation in nude mice. In contrast, comparable levels of two TS mutants carrying single point mutations within the catalytic domain had no transforming activity. In addition, we show that overexpression of TS results in apoptotic cell death following serum removal. These data demonstrate that TS exhibits oncogene-like activity and suggest a link between TS-regulated DNA synthesis and the induction of a neoplastic phenotype.

引用

页码：341 / 351

页数：11

共 56 条

[21] Ribonucleotide reductase R2 component is a novel malignancy determinant that cooperates with activated oncogenes to determine transformation and malignant potential [J].