Analysis of the cyclin-dependent kinase inhibitor p27Kip1 in muscle invasive bladder cancer.
It has been suggested that a deregulated cell cycle control contributes to the development of human malignancies due to the loss of critical antiproliferative mechanisms. The cell cycle is controlled at two checkpoints, one at the G1-S and another at the G2-M transition. Several genes including the structurally related p21WAF/CIP1 gene, the downstream mediator of the p53 tumor suppressor gene, and the p27Kip1 gene have been identified as inducers of cell cycle arrest at the G1 checkpoint when substantial DNA damage has occurred to avoid further replication of the altered genome. Recently, a heat stable 27 kDa protein, the transcript of the p27Kip1 gene, has been identified and was suggested to substantially participate in cell cycle control at the G1 checkpoint. Previous investigations have correlated decreased expression of the p27Kip1 protein with an increased biological aggressiveness of breast and small cell lung cancer. However, the molecular-genetic analysis of a variety of human malignancies including prostate cancer failed to identify any alteration at the p27Kip1 gene locus, therefore suggesting a loss of p27Kip1 protein expression to result from post-transcriptional/post-translational events or from so far unknown regulatory mechanisms. So far, bladder cancer specimens have neither been investigated for p27Kip1 alterations on the DNA level, nor has the result of molecular genetic analysis been correlated with an immunohistochemically detected expression of the gene product, the p27Kip1 protein. The present study is the first to describe p27Kip1 gene alterations on the DNA level in 3 of 42 muscle invasive bladder cancer specimens. In contrast, loss of p27Kip1 protein expression was observed in 14 of 42 (33%) tumors. According to the previously reported observation in a variety of human malignancies, in bladder cancer loss of p27Kip1 protein expression seems to result from post-transcriptional or post-translational events.
Serth
J
J
Department of Urology, Hannover University Medical School, Hannover, Germany.
Kuczyk
M
M
Machtens
S
S
Bokemeyer
C
C
Herrmann
R
R
Hartmann
J
J
Knüchel
R
R
Jonas
U
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016193:G1 Phase; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D017354:Point Mutation; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27