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Overexpression of CDC25A and CDC25B in head and neck cancers.

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TLDR
The expression of CDC25A, CDC25B, and CDC25C genes in 20 squamous cell carcinomas of the head and neck are analyzed by quantitative reverse transcription-PCR on the basis of the evidence that CDC25 phosphatases can act as oncogenes.
Abstract
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.

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Journal ArticleDOI

CDC25 phosphatases in cancer cells: key players? Good targets?

TL;DR: The roles of CDC25 phosphatases in both normal and abnormal cell proliferation are focused on, a critical assessment of the current data on CDC25 overexpression in cancer is provided, and both current and future therapeutic strategies for targeting CDC25 activity in cancer treatment are discussed.
Journal ArticleDOI

Pathways governing G1/S transition and their response to DNA damage

Jiri Bartek, +1 more
- 16 Feb 2001 - 
TL;DR: Recent advances in understanding the molecular pathways which govern the decision of mammalian somatic cells to enter S phase are highlighted, and the so‐called cell cycle checkpoints which guard the G1/S transition and S phase progression against potentially deleterious effects of genotoxic stress are highlighted.
Book ChapterDOI

Cell cycle regulation by the Cdc25 phosphatase family.

TL;DR: Cdc25 is a main player of the G2 arrest caused by DNA damage or in the presence of unreplicated DNA and potential human oncogenes, and plays a role in activating the mitotic kinase Cdk1/cycl in the cytoplasm.
Journal ArticleDOI

MAPKAP Kinase-2 Is a Cell Cycle Checkpoint Kinase that Regulates the G2/M Transition and S Phase Progression in Response to UV Irradiation

TL;DR: It is proposed that MAPKAP kinase-2 is a new member of the DNA damage checkpoint kinase family that functions in parallel with Chk1 and Chk2 to integrate DNA damage signaling responses and cell cycle arrest in mammalian cells.
Journal ArticleDOI

Regulation of G2/M events by Cdc25A through phosphorylation‐dependent modulation of its stability

TL;DR: A distinct, markedly stable form of Cdc25A is described, which plays a previously unrecognized role in mitosis, and phosphorylation‐mediated switches among three differentially stable forms ensure distinct thresholds, and thereby distinct roles for CDC25A in multiple cell cycle transitions and checkpoints.
References
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TL;DR: In this paper, complementary oligodeoxyribonucleotide (oligo) primers and the polymerase chain reaction are used to generate two DNA fragments having overlapping ends, and these fragments are combined in a subsequent 'fusion' reaction in which the overlapping ends anneal, allowing the 3' overlap of each strand to serve as a primer for the three' extension of the complementary strand.
Journal ArticleDOI

Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction

TL;DR: An adaptation of the polymerase chain reaction (PCR) for highly accurate quantitation of mRNA or DNA from a small number of cells for expression of two cytokines and the copy number of the human GM-CSF gene in normal human cells is described.
Journal ArticleDOI

Cdc25 cell-cycle phosphatase as a target of c- myc

TL;DR: Findings indicate that cdc25A is a physiologically relevant transcriptional target of c-myc, a proto-oncogene that can promote either oncogenic transformation or apoptosis in cells depleted of growth factor.
Journal Article

High Frequency of p16 (CDKN2/MTS-1/INK4A) Inactivation in Head and Neck Squamous Cell Carcinoma

TL;DR: The data suggest that inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and immunohistochemical analysis for expression of thep16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.
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