OVEREXPRESSION OF CDC25A AND CDC25B IS FREQUENT IN PRIMARY NONSMALL CELL LUNG-CANCER BUT IS NOT ASSOCIATED WITH OVEREXPRESSION OF C-MYC

Cyclin-dependent kinases can be activated by cdc25, which removes inhi bitory phosphates from tyrosine and threonine residues, At least three cdc25 genes (cdc25A, cdc25B, and cdc25C) have been identified in huma ns. Accumulating evidence indicates that cdc25A and cdc25B possess onc ogenic properties. Recently, overexpression of cdc25A and of cdc25B wa s found in many breast and head and neck cancers, To determine potenti al 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% (2 4 of 40) of the tumors and cdc25B in 45% (18 of 40) of the tumors, whe reas cdc25C was not overexpressed in any of the tumors analyzed, Becau se c-myc can increase cdc25A and cdc25B expression, it may be a factor in cdc25 overexpression, We found that c-myc was overexpressed in onl y 18% (7 of 40) of the tumors. We found no association between overexp ression of c-myc and cdc25A or cdc25B, We also investigated whether th e 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 corr elated with gene expression status, Interestingly, among 24 tumors wit h 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 frequenc ies of cdc25A and cdc25B overexpression [19% (3 of 16) and 23% (5 of 2 2), respectively]. These data indicate that overexpression of cdc25A a nd 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 s timulation or cdc25B gene amplification.