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      CDC25 phosphatases as potential human oncogenes.

      Science (New York, N.Y.)
      Animals, Breast Neoplasms, genetics, Cell Cycle Proteins, Cell Division, Cell Transformation, Neoplastic, Cells, Cultured, Gene Expression, Genes, Retinoblastoma, Genes, p53, Genes, ras, Humans, In Situ Hybridization, Mice, Mice, Inbred BALB C, Mice, Nude, Multigene Family, Neoplasm Transplantation, Oncogenes, Phosphoprotein Phosphatases, Prognosis, Transfection, Tumor Cells, Cultured, cdc25 Phosphatases

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          Abstract

          Cyclin-dependent kinases (CDKs) are activated by CDC25 phosphatases, which remove inhibitory phosphate from tyrosine and threonine residues. In human cells, CDC25 proteins are encoded by a multigene family, consisting of CDC25A, CDC25B, and CDC25C. In rodent cells, human CDC25A or CDC25B but not CDC25C phosphatases cooperate with either Ha-RASG12V or loss of RB1 in oncogenic focus formation. Such transformants were highly aneuploid, grew in soft agar, and formed high-grade tumors in nude mice. Overexpression of CDC25B was detected in 32 percent of human primary breast cancers tested. The CDC25 phosphatases may contribute to the development of human cancer.

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