Mutational analysis defines a minimum level of telomerase activity required for tumourigenic growth of human cells.

A hallmark of cancer cells is the ability to proliferate indefinitely. This acquisition of an immortal lifespan usually requires the activation of telomerase, the enzyme that elongates telomeres. Human telomerase is minimally composed of the reverse transcriptase subunit hTERT, and the RNA subunit hTR.

Distinct requirements for Ras oncogenesis in human versus mouse cells.

The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector proteins, Rafs, PI3-kinase, and RalGEFs, with Raf generally being the most potent at transforming murine cells. Using oncogenic Ras mutants that activate single effectors as well as constitutively active effectors, we find that the RalGEF, and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in human cells.