p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors
Ponce-Castañeda, M.V.; Lee, M.H.; Latres, E.; Polyak, K.; Lacombe, L.; Montgomery, K.; Mathew, S.; Krauter, K.; Sheinfeld, J.; Massague, J.
Cancer Research 55(6): 1211-1214
1995
ISSN/ISBN: 0008-5472 PMID: 7882310 Document Number: 439423
The p27-kipa gene codes for a cyclin-dependent kinase inhibitor implicated in G-1 arrest by transforming growth factor beta, 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 p27-Kip1 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 p27-Kip1 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 beta responsiveness in human cancer cells is not due to structural defects in p27-Kip1.