Mutation and expression analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in pituitary tumors.
By regulating cyclin-cyclin-dependent kinase (CDK) complex activity, individual CDK inhibitors (CDKIs) are potential tumor suppressors. One of the CDKIs, p27/Kip1, binds to a variety of CDK-cyclin complexes. A link between loss of p27/Kip1 function and development of pituitary tumors was suggested by the formation of pituitary tumors in almost all mice with germline deletion of the p27/Kip1 gene. However, genetic aberrations in the p27/Kip1 locus have not been analyzed in human pituitary tumors. We investigated eighteen non-functioning and GH-secreting pituitary tumor samples for p27/Kip1 mutations by single-strand conformational polymorphism (SSCP) following PCR. We found five abnormally migrating samples on the PCR-SSCP analysis. The sequence of these samples revealed a polymorphism of codon 109 (Val-->Gly), which has been previously described. No other structural changes of p27/Kip1 were found in these pituitary tumors within the coding region. In addition, no difference in p27/Kip1 protein levels in pituitary tumor tissues compared with normal pituitary tissues was demonstrated by immunostaining. These data suggest that both p27/Kip1 mutations and decreases in p27/Kip1 protein levels are infrequent in the development of pituitary tumors.
Takeuchi
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S
Department of Medicine, Cedars-Sinai Research Institute, UCLA School of Medicine 90048, USA.
Koeffler
H P
HP
Hinton
D R
DR
Miyoshi
I
I
Melmed
S
S
Shimon
I
I
D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000032:analysis; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases