cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.
cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.
Hernández
S
S
Department of Pathology, Institut de Investigacions Biomèdiques Agustí Pí i Sunyer, University of Barcelona, Spain.
Hernández
L
L
Beà
S
S
Cazorla
M
M
Fernández
P L
PL
Nadal
A
A
Muntané
J
J
Mallofré
C
C
Montserrat
E
E
Cardesa
A
A
Campo
E
E
D015152:Blotting, Northern; D015139:Blotting, Southern; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D010749:Phosphoprotein Phosphatases; C517004:CDC25A protein, human; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases