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Genomic Integrity and the Genetics of Cancer

1994; Cold Spring Harbor Laboratory Press; Volume: 59; Linguagem: Inglês

10.1101/sqb.1994.059.01.031

1943-4456

Thea D. Tlsty, Anne White, Elizabeth Livanos, Marijke Sage, Helene Roelofs, Amy Briot, Benjamin K. Poulose,

RNA modifications and cancer

One method of maintaining genomic integrity involves the action of cell cycle checkpoint genes. These genes integrate proper sensing of environmental signals and appropriate cellular responses. Recent work suggests that p53 performs such an integrator function in mammalian cells. In this paper, we describe how, in mortal cells, the E6 and E7 viral oncoproteins of type 16 human papillomavirus (HPV) each disrupts the integration of these signals in its own unique way, resulting in two distinct types of genomic alterations and cell death as the cells respond to negative growth signals. Furthermore, these alterations in response to negative growth signals can precede any overt phenotypes displayed by the oncoprotein-expressing cells and suggest a novel way to examine cells from individuals that are predisposed to malignancy. These studies implicate loss of cell cycle control in tumor progression.