Lack of p16INK4 or retinoblastoma protein (pRb), or amplification-associated overexpression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines.
In this study the expression of p16INK4, retinoblastoma protein (pRb), and cdk4 proteins have been examined in 18 malignant glioma cell lines and in 45 malignant glial tumors. Loss of p16INK4 expression associated with p16INK4 gene homozygous deletion was evident in 12 cell lines and in 10 primary tumors. Lack of p16INK4 expression was also evident in five tumors for which there was no evidence of p16INK4 gene homozygous deletion. Two of the cell lines and six of the primary tumors in which p16INK4 was present were determined to overexpress cdk4 in association with CDK4 gene amplification. Absence of pRb was determined in two of the cell lines and in ten of the tumors. In total, 16 of 18 cell lines and 25 of 45 tumors showed either a lack of p16INK4 or pRb or amplification-associated overexpression of cdk4. Two additional tumors showed an absence of pRb and p16INK4, and one tumor showed a lack of pRb combined with amplification-associated overexpression of cdk4. These results suggest a common growth-regulatory mechanism that is disrupted in gliomas by either suppressing the expression of p16INK4 or pRb or by increasing the expression of cdk4.
He
J
J
Department of Neurosurgery, Emory University, Atlanta, Georgia 30322, USA.
Olson
J J
JJ
James
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CD
D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D005784:Gene Amplification; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases