title: Overexpression of cdc25A and cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc.
abstract: Cyclin-dependent kinases can be activated by cdc25, which removes inhibitory phosphates from tyrosine and threonine residues. At least three cdc25 genes (cdc25A, cdc25B, and cdc25C) have been identified in humans. Accumulating evidence indicates that cdc25A and cdc25B possess oncogenic properties. Recently, overexpression of cdc25A and of cdc25B was found in many breast and head and neck cancers. To determine potential roles of cdc25s in non-small cell lung cancer (NSCLC), we analyzed primary tumors and corresponding normal lung tissues from 40 patients with NSCLC for relative expression levels of these genes by multiplex reverse transcription PCR (RT-PCR). cdc25A was overexpressed in 60% (24 of 40) of the tumors and cdc25B in 45% (18 of 40) of the tumors, whereas cdc25C was not overexpressed in any of the tumors analyzed. Because c-myc can increase cdc25A and cdc25B expression, it may be a factor in cdc25 overexpression. We found that c-myc was overexpressed in only 18% (7 of 40) of the tumors. We found no association between overexpression of c-myc and cdc25A or cdc25B. We also investigated whether the cdc25B gene was amplified in NSCLC and found this was true in 40% (8 of 20) of the tumors tested. However, this amplification was not correlated with gene expression status. Interestingly, among 24 tumors with cdc25A overexpression and 18 with cdc25B overexpression, 42% (10 of 24) and 44% (8 of 18) were poorly differentiated histological type. In contrast, well or moderately differentiated tumors had lower frequencies of cdc25A and cdc25B overexpression [19% (3 of 16) and 23% (5 of 22), respectively]. These data indicate that overexpression of cdc25A and cdc25B is frequent and that it may play an important role in NSCLC. However, it is unlikely that this overexpression is caused by c-myc stimulation or cdc25B gene amplification.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: Y H
authors.initials: YH
authors.lastname: Fan
authors.forename: B L
authors.initials: BL
authors.lastname: Kemp
authors.forename: G
authors.initials: G
authors.lastname: Walsh
authors.forename: L
authors.initials: L
authors.lastname: Mao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020687:cdc25 Phosphatases
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D010749:Phosphoprotein Phosphatases; C517004:CDC25A protein, human; C517008:CDC25B protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases