Abstract: |
The p27Kip1 gene codes for a cyclin-dependent kinase inhibitor implicated in G1 arrest by transforming growth factor β, cell-cell contact, agents that elevate cyclic AMP, and the growth-inhibitory drug rapamycin. p27 binds to and inhibits complexes formed by cyclin E-cdk2, cyclin A-cdk2, and cyclin D-cdk4. The involvement of p27 in the negative regulation of cell proliferation suggests that it may also function as a tumor suppressor gene. Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27kip1 has been mapped to the short arm of chromosome 12 at the 12p12–12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas. In order to assess potential p27Kip1 gene alterations, we have screened a total of 147 human primary solid tumors and found no detectable cancer-specific mutations. These results argue that the often observed loss of antimitogenic transforming growth factor β responsiveness in human cancer cells is not due to structural defects in p27Kip1. © 1995, American Association for Cancer Research. All rights reserved. |
Keywords: |
controlled study; human tissue; leukemia; genetics; mutation; molecular genetics; polymerase chain reaction; neoplasm; neoplasms; cell proliferation; chromosome 12; protein kinases; transforming growth factor beta; fluorescence; enzyme inhibitor; in situ hybridization; tumor suppressor gene; dna; molecular sequence data; nucleotide sequence; cancer cell; mesothelioma; cyclic amp; base sequence; dna sequence; cycline; tumor; cyclins; cyclin dependent kinase; protein kinase; rapamycin; chromosome 12p; chromosome map; chromosome mapping; southern blotting; agar gel electrophoresis; hybrid cell; chromosomes, human, pair 12; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; cip1 protein
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