The Genetic and Molecular Basis of Gastrointestinal and Liver Diseases



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Oncogenes: Cyclins and Cyclin-dependent Kinases

Two examples of oncogenes implicated in Barrett’s esophagus are cyclins D1 and E. Phosphorylation of Rb occurs by interactions with cyclin-dependent kinases (cdks) and cyclins.  Cdks are the enzymes responsible for the phosphorylation of Rb whereas cyclins carry the cdks to their targets. By phosphorylating and inactivating Rb, cdks and cyclins regulate the transition from G1 to S phase.  Increased cyclin D1, but not E, protein has been detected in biopsy specimens of non-dysplastic Barrett’s metaplasia. Overexpression of cyclin E has been found in both low-grade and high-grade dysplastic areas of Barrett’s esophagus as well as in adenocarcinomas.

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Arber N, Lightdale C, Rotterdam H, et al.  Increased expression of the cyclin D1 gene in Barrett's esophagus. Cancer Epidemiol Biomarkers Prev 1996;5:457-459.

Sarbia M, Bektas N, Muller W, et al.  Expression of cyclin E in dysplasia, carcinoma, and nonmalignant lesions of Barrett esophagus. Cancer 1999;86:2597-2601.