Overexpression of CDC25A and CDC25B in head and neck cancers.
The deregulation of several cell cycle-related genes participates in neoplastic transformation. Cell cycle progression is driven by cyclin-dependent kinases, which are positively regulated by association with cyclins and negatively regulated by binding to inhibitory subunits. The activity of cyclin-dependent kinases is also regulated by the phosphorylation status, which is controlled by the antagonistic action of wee1 kinase and CDC25 phosphatases. Three CDC25 genes are present in human cells: CDC25A, CDC25B, and CDC25C. These three genes function at different phases of the cell cycle. Whereas CDC25A and CDC25B are expressed throughout the cell cycle, with peak expression in G1 for CDC25A and in both G1-S-phase and G2 for CDC25B, CDC25C is predominantly expressed in G2. Several lines of evidence suggest a role for CDC25s as oncogenes. CDC25A and CDC25B cooperate with Ha-ras or loss of Rb1 in the oncogenic transformation of rodent fibroblasts. Moreover, they are transcriptional targets of c-myc, and CDC25A in particular plays an important role as a mediator of myc functions. On the basis of the evidence that CDC25 phosphatases can act as oncogenes, we analyzed the expression of CDC25A, CDC25B, and CDC25C genes in 20 squamous cell carcinomas of the head and neck by quantitative reverse transcription-PCR. Our results show that whereas CDC25C is expressed at a low level with no relevant differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are overexpressed in a large fraction of tumors.
Gasparotto
D
D
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.
Maestro
R
R
Piccinin
S
S
Vukosavljevic
T
T
Barzan
L
L
Sulfaro
S
S
Boiocchi
M
M
D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D010749:Phosphoprotein Phosphatases; C517004:CDC25A protein, human; C517008:CDC25B protein, human; C517009:CDC25C protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases