Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors.
p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP2 is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57KIP2 is imprinted in the mouse. Here we describe the genomic imprinting of human p57KIP2 and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57KIP2 in the region responsible for both tumor suppressivity and BWS.
Hatada
I
I
National Cardiovascular Center Research Institute, Osaka, Japan.
Inazawa
J
J
Abe
T
T
Nakayama
M
M
Kaneko
Y
Y
Jinno
Y
Y
Niikawa
N
N
Ohashi
H
H
Fukushima
Y
Y
Iida
K
K
Yutani
C
C
Takahashi
S
S
Chiba
Y
Y
Ohishi
S
S
Mukai
T
T
D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004247:DNA; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D004247:DNA