Cyclin-dependent kinase inhibitor p57KIP2 in soft tissue sarcomas and Wilms' tumors

Irene Orlow, Antonio Iavarone, Shyra J. Crider-Miller, Félix Bonilla, Esther Latres, Mong Hong Lee, William L. Gerald, Joan Massagué, Bernard E. Weissman, Carlos Cordón-Cardó

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48 Scopus citations

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.

Original languageEnglish
Pages (from-to)1219-1221
Number of pages3
JournalCancer Research
Volume56
Issue number6
StatePublished - 15 Mar 1996
Externally publishedYes

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