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Induction of Cdc25B expression by epidermal growth factor and transforming growth factor-α

Oguri, T and Nemoto, K and Bansal, P and Wipf, P and Lazo, JS (2004) Induction of Cdc25B expression by epidermal growth factor and transforming growth factor-α. Biochemical Pharmacology, 68 (11). 2221 - 2227. ISSN 0006-2952

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The dual specificity protein phosphatase Cdc25B regulates of the mitotic cell cycle checkpoint and is over expressed in human tumors. Given the importance of growth factors in initiating and sustaining cell proliferation, we examined their effects on Cdc25B protein expression in human cancer cells. Within 1 h after epidermal growth factor (EGF) or transforming growth factor-α (TGF-α) treatment, Cdc25B protein levels increased in growth factor responsive A549 and SCC25 cells, but not in non-responsive MDA-MB-231 cells. A functional consequence of elevated Cdc25B was implied by the concomitant decrease in phosphorylated cyclin dependent kinase, a known Cdc25B substrate, after growth factor treatment of A549 and SCC25 cells. The EGF-mediated induction of Cdc25B required a functional EGF receptor (ErbB1), as mouse embryonic fibroblasts lacking ErbB1 did not have increased Cdc25B levels after EGF treatment. Moreover, the EGFR receptor-selective tyrosine kinase inhibitor AG1478 and mitogen activated kinase kinase inhibitor U0126 blocked growth factor-mediated Cdc25B induction. Thus, EGF and TGF-α appear to induce cellular Cdc25B through the mitogen-activated protein kinase pathway. © 2004 Elsevier Inc. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Oguri, T
Nemoto, K
Bansal, P
Wipf, Ppwipf@pitt.eduPWIPF
Lazo, JS
Date: 1 December 2004
Date Type: Publication
Journal or Publication Title: Biochemical Pharmacology
Volume: 68
Number: 11
Page Range: 2221 - 2227
DOI or Unique Handle: 10.1016/j.bcp.2004.08.011
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0006-2952
MeSH Headings: Butadienes--pharmacology; Cell Cycle Proteins--genetics; Cell Cycle Proteins--metabolism; Enzyme Inhibitors--pharmacology; Epidermal Growth Factor--pharmacology; Gene Expression--drug effects; Humans; Nitriles--pharmacology; Transforming Growth Factor alpha--pharmacology; Tumor Cells, Cultured; cdc25 Phosphatases--genetics; cdc25 Phosphatases--metabolism
PubMed ID: 15498512
Date Deposited: 30 Jan 2014 18:13
Last Modified: 02 Feb 2019 15:57


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