title: p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors.
abstract: The p27Kip1 gene codes for a cyclin-dependent kinase inhibitor implicated in G1 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 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 beta responsiveness in human cancer cells is not due to structural defects in p27Kip1.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M V
authors.initials: MV
authors.lastname: Ponce-Castañeda
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Latres
authors.forename: K
authors.initials: K
authors.lastname: Polyak
authors.forename: L
authors.initials: L
authors.lastname: Lacombe
authors.forename: K
authors.initials: K
authors.lastname: Montgomery
authors.forename: S
authors.initials: S
authors.lastname: Mathew
authors.forename: K
authors.initials: K
authors.lastname: Krauter
authors.forename: J
authors.initials: J
authors.lastname: Sheinfeld
authors.forename: J
authors.initials: J
authors.lastname: Massague
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D047428:Protein Kinase Inhibitors
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047428:Protein Kinase Inhibitors