PT  - JOURNAL ARTICLE
AU  - Fan, Huizhou
AU  - Villegas, Cristy
AU  - Huang, Aiping
AU  - Wright, Jim A.
TI  - The Mammalian Ribonucleotide Reductase R2 Component Cooperates with a Variety of Oncogenes in Mechanisms of Cellular Transformation
DP  - 1998 Apr 15
TA  - Cancer Research
PG  - 1650--1653
VI  - 58
IP  - 8
4099  - http://cancerres.aacrjournals.org/content/58/8/1650.short
4100  - http://cancerres.aacrjournals.org/content/58/8/1650.full
SO  - Cancer Res1998 Apr 15; 58
AB  - Ribonucleotide reductase, which is composed of the two protein components R1 and R2, is a highly regulated enzyme activity that is essential for DNA synthesis and repair. Recent studies have shown that elevated expression of the rate-limiting R2 component increases Raf-1 protein activation and mitogen-activated protein kinase activity and acts as a novel malignancy determinant in cooperation with H-ras and rac-1. We show that R2 cooperation in cellular transformation extends to a variety of oncogenes with different functions and cellular locations. Anchorage-independent growth of cells transformed with v-fms, v-src, A-raf, v-fes, c-myc, and ornithine decarboxylase was markedly enhanced when the R2 component of ribonucleotide reductase was overexpressed. In addition, we observed that elevated R2 expression conferred on c-myc-transformed NIH 3T3 cells an increased tumorigenic potential in immunoincompetent mice. Taken together, these observations demonstrate that the R2 protein is not only a rate-limiting component for ribonucleotide reduction but that it is also capable of acting in cooperation with a variety of oncogenes to determine transformation and tumorigenic potential. ©1998 American Association for Cancer Research.