Cyclin-dependent kinase inhibitor p57(KIP2) in soft tissue sarcomas and Wilms' tumors Journal Article


Authors: Orlow, I.; Iavarone, A.; Crider-Miller, S. J.; Bonilla, F.; Latres, E.; Lee, M. H.; Gerald, W. L.; Massagué, J.; Weissman, B. E.; Cordón-Cardó, C.
Article Title: Cyclin-dependent kinase inhibitor p57(KIP2) in soft tissue sarcomas and Wilms' tumors
Abstract: Mammalian cyclin-dependent kinase inhibitors fall into two families, the INK4 and the CIP/KIP. The CIP/KIP family comprises three structurally related members, including p21CIP1/WAF1, p27KIF1, and p57KIP2. These proteins are all capable of inhibiting the progression of the cell cycle by binding and inhibiting G1 cyclin/cyclin-dependent kinase complexes. In humans, p57KIP2 is expressed specifically in skeletal muscle, heart, brain, kidney, and lung. Human KIP2 resides in 11p15.5, a chromosomal region that is a common site for loss of heterozygosity in certain sarcomas, Wilms' tumors, and tumors associated with the Beckwith-Wiedemann syndrome. Because of the function, selective expression, and chromosomal location of p57KIP2, we undertook the present study to search for potential mutations of KIP2 in a cohort of 126 tumors composed of 75 soft tissue sarcomas and 51 Wilms' tumors. The KIP2 gene was characterized by Southern blot, comparative multiplex PCR, PCR-single-strand conformational polymorphism, and DNA sequencing assays in these neoplasms. Deletions of the KIP2 gene or point mutations at the region encoding the cyclin-dependent kinase inhibitory domain were not found in the tumors analyzed. The absence of KIP2 mutations might indicate that these tumors arise due to defects at a closely linked but separate locus. Alternatively, similarly to the mouse homologue, inactivation of KIP2 could occur via genomic imprinting.
Keywords: adult; child; protein expression; major clinical study; gene deletion; polymerase chain reaction; protein localization; protein analysis; neoplasm proteins; enzyme inhibitor; kidney neoplasms; nuclear proteins; sarcoma; cancer genetics; molecular sequence data; tissue distribution; soft tissue sarcoma; base sequence; dna sequence; point mutation; cyclin dependent kinase; chromosomes, human, pair 11; genes, tumor suppressor; nephroblastoma; wilms tumor; single strand conformation polymorphism; genes, wilms tumor; cyclin-dependent kinase inhibitor p57; humans; human; priority journal; article
Journal Title: Cancer Research
Volume: 56
Issue: 6
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1996-03-15
Start Page: 1219
End Page: 1221
Language: English
PUBMED: 8640801
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. William L Gerald
    375 Gerald
  2. Irene Orlow
    247 Orlow
  3. Joan Massague
    389 Massague
  4. Mong-Hong Lee
    15 Lee
  5. Esther Latres
    10 Latres